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Sample records for notochord morphogenesis vertebral

  1. Ascidian notochord morphogenesis

    PubMed Central

    Jiang, Di; Smith, William C.

    2010-01-01

    The development of the notochord involves a complex set of cellular behaviors. While these morphogenic behaviors are common to all chordates, the ascidian provides a particularly attractive experimental model because of its relative simplicity. In particular, all notochord morphogenesis in ascidians takes place with only 40 cells, as opposed to the hundreds of cells in vertebrate models systems. Initial steps in ascidian notochord development convert a monolayer of epithelial-like cells in the pre-gastrula embryo to a cylindrical rod of single-cell diameter. Convergent extension is responsible for the intercalation of notochord cells and some degree of notochord elongation, while a second phase of elongation is observed as the notochord narrows medially and increases in volume. The mechanism by which the volume of the notochord increases differs between ascidian species. Some ascidian species produce extracellular pockets that will eventually coalesce to form a lumen running the length of the notochord, while others appear to make intercellular vacuoles. By either mechanism, the resulting notochord serves as a hydrostatic skeleton allowing for the locomotion of the swimming larva. Several basic cell behaviors, such as cell shape changes, cell rearrangement, establishment of cell polarity, and alteration of extracellular environment, are displayed in the process of notochord morphogenesis. Modern analysis of ascidian notochord morphogenesis promises to contribute to our understanding of these fundamental biological processes. PMID:17497687

  2. Notochord vacuoles are lysosome-related organelles that function in axis and spine morphogenesis

    PubMed Central

    Ellis, Kathryn; Bagwell, Jennifer

    2013-01-01

    The notochord plays critical structural and signaling roles during vertebrate development. At the center of the vertebrate notochord is a large fluid-filled organelle, the notochord vacuole. Although these highly conserved intracellular structures have been described for decades, little is known about the molecular mechanisms involved in their biogenesis and maintenance. Here we show that zebrafish notochord vacuoles are specialized lysosome-related organelles whose formation and maintenance requires late endosomal trafficking regulated by the vacuole-specific Rab32a and H+-ATPase–dependent acidification. We establish that notochord vacuoles are required for body axis elongation during embryonic development and identify a novel role in spine morphogenesis. Thus, the vertebrate notochord plays important structural roles beyond early development. PMID:23460678

  3. Notochord vacuoles are lysosome-related organelles that function in axis and spine morphogenesis.

    PubMed

    Ellis, Kathryn; Bagwell, Jennifer; Bagnat, Michel

    2013-03-01

    The notochord plays critical structural and signaling roles during vertebrate development. At the center of the vertebrate notochord is a large fluid-filled organelle, the notochord vacuole. Although these highly conserved intracellular structures have been described for decades, little is known about the molecular mechanisms involved in their biogenesis and maintenance. Here we show that zebrafish notochord vacuoles are specialized lysosome-related organelles whose formation and maintenance requires late endosomal trafficking regulated by the vacuole-specific Rab32a and H(+)-ATPase-dependent acidification. We establish that notochord vacuoles are required for body axis elongation during embryonic development and identify a novel role in spine morphogenesis. Thus, the vertebrate notochord plays important structural roles beyond early development.

  4. Notochord morphogenesis in mice: Current understanding & open questions.

    PubMed

    Balmer, Sophie; Nowotschin, Sonja; Hadjantonakis, Anna-Katerina

    2016-05-01

    The notochord is a structure common to all chordates, and the feature that the phylum Chordata has been named after. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Yet, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary, we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. Developmental Dynamics 245:547-557, 2016. © 2016 Wiley Periodicals, Inc. PMID:26845388

  5. A central role for the notochord in vertebral patterning.

    PubMed

    Fleming, Angeleen; Keynes, Roger; Tannahill, David

    2004-02-01

    The vertebrates are defined by their segmented vertebral column, and vertebral periodicity is thought to originate from embryonic segments, the somites. According to the widely accepted 'resegmentation' model, a single vertebra forms from the recombination of the anterior and posterior halves of two adjacent sclerotomes on both sides of the embryo. Although there is supporting evidence for this model in amniotes, it remains uncertain whether it applies to all vertebrates. To explore this, we have investigated vertebral patterning in the zebrafish. Surprisingly, we find that vertebral bodies (centra) arise by secretion of bone matrix from the notochord rather than somites; centra do not form via a cartilage intermediate stage, nor do they contain osteoblasts. Moreover, isolated, cultured notochords secrete bone matrix in vitro, and ablation of notochord cells at segmentally reiterated positions in vivo prevents the formation of centra. Analysis of fss mutant embryos, in which sclerotome segmentation is disrupted, shows that whereas neural arch segmentation is also disrupted, centrum development proceeds normally. These findings suggest that the notochord plays a key, perhaps ancient, role in the segmental patterning of vertebrae.

  6. Chemical genetics suggests a critical role for lysyl oxidase in zebrafish notochord morphogenesis.

    PubMed

    Anderson, Carrie; Bartlett, Stephen J; Gansner, John M; Wilson, Duncan; He, Ling; Gitlin, Jonathan D; Kelsh, Robert N; Dowden, James

    2007-01-01

    As a result of a chemical genetic screen for modulators of metalloprotease activity, we report that 2-mercaptopyridine-N-oxide induces a conspicuous undulating notochord defect in zebrafish embryos, a phenocopy of the leviathan mutant. The location of the chemically-induced wavy notochord correlated with the timing of application, thus defining a narrow chemical sensitivity window during segmentation stages. Microscopic observations revealed that notochord undulations appeared during the phase of notochord cell vacuolation and notochord elongation. Notochord cells become swollen as well as disorganized, while electron microscopy revealed disrupted organization of collagen fibrils in the surrounding sheath. We demonstrate by assay in zebrafish extracts that 2-mercaptopyridine-N-oxide inhibits lysyl oxidase. Thus, we provide insight into notochord morphogenesis and reveal novel compounds for lysyl oxidase inhibition. Taken together, these data underline the utility of small molecules for elucidating the dynamic mechanisms of early morphogenesis and provide a potential explanation for the recently established role of copper in zebrafish notochord formation.

  7. Planar Cell Polarity in vertebrate limb morphogenesis

    PubMed Central

    Gao, Bo; Yang, Yingzi

    2013-01-01

    Studies of the vertebrate limb development have contributed significantly to understanding the fundamental mechanisms underlying growth, patterning and morphogenesis of a complex multicellular organism. In the limb, well-defined signaling centers interact to coordinate limb growth and patterning along the three axes. Recent analyses of live imaging and mathematical modeling have provided evidence that polarized cell behaviors governed by morphogen gradients play an important role in shaping the limb bud. Furthermore, the Wnt/Planar Cell Polarity (PCP) pathway that controls uniformly polarized cellular behaviors in a field of cells has emerged to be critical for directional morphogenesis in the developing limb. Directional information coded in the morphogen gradient may be interpreted by responding cells through regulating the activities of PCP components in a Wnt morphogen dose-dependent manner. PMID:23747034

  8. Microtubules, polarity and vertebrate neural tube morphogenesis.

    PubMed

    Cearns, Michael D; Escuin, Sarah; Alexandre, Paula; Greene, Nicholas D E; Copp, Andrew J

    2016-07-01

    Microtubules (MTs) are key cellular components, long known to participate in morphogenetic events that shape the developing embryo. However, the links between the cellular functions of MTs, their effects on cell shape and polarity, and their role in large-scale morphogenesis remain poorly understood. Here, these relationships were examined with respect to two strategies for generating the vertebrate neural tube: bending and closure of the mammalian neural plate; and cavitation of the teleost neural rod. The latter process has been compared with 'secondary' neurulation that generates the caudal spinal cord in mammals. MTs align along the apico-basal axis of the mammalian neuroepithelium early in neural tube closure, participating functionally in interkinetic nuclear migration, which indirectly impacts on cell shape. Whether MTs play other functional roles in mammalian neurulation remains unclear. In the zebrafish, MTs are important for defining the neural rod midline prior to its cavitation, both by localizing apical proteins at the tissue midline and by orienting cell division through a mirror-symmetric MT apparatus that helps to further define the medial localization of apical polarity proteins. Par proteins have been implicated in centrosome positioning in neuroepithelia as well as in the control of polarized morphogenetic movements in the neural rod. Understanding of MT functions during early nervous system development has so far been limited, partly by techniques that fail to distinguish 'cause' from 'effect'. Future developments will likely rely on novel ways to selectively impair MT function in order to investigate the roles they play.

  9. Cells, molecules and morphogenesis: The making of the vertebrate ear

    PubMed Central

    Fritzsch, Bernd; Pauley, Sarah; Beisel, Kirk W.

    2014-01-01

    The development and evolution of mechanosensory cells and the vertebrate ear is reviewed with an emphasis on delineating the cellular, molecular and developmental basis of these changes. Outgroup comparisons suggests that mechanosensory cells are ancient features of multicellular organisms. Molecular evidence suggests that key genes involved in mechanosensory cell function and development are also conserved among metazoans. The divergent morphology of mechanosensory cells across phyla is interpreted here as ‘deep molecular homology’ that was in parallel shaped into different forms in each lineage. The vertebrate mechanosensory hair cell and its associated neuron are interpreted as uniquely derived features of vertebrates. It is proposed that the vertebrate otic placode presents a unique embryonic adaptation in which the diffusely distributed ancestral mechanosensory cells became concentrated to generate a large neurosensory precursor population. Morphogenesis of the inner ear is reviewed and shown to depend on genes expressed in and around the hindbrain that interact with the otic placode to define boundaries and polarities. These patterning genes affect downstream genes needed to maintain proliferation and to execute ear morphogenesis. We propose that fibroblast growth factors (FGFs) and their receptors (FGFRs) are a crucial central node to translate patterning into the complex morphology of the vertebrate ear. Unfortunately, the FGF and FGFR genes have not been fully analyzed in the many mutants with morphogenetic ear defects described thus far. Likewise, little information exists on the ear histogenesis and neurogenesis in many mutants. Nevertheless, a molecular mechanism is now emerging for the formation of the horizontal canal, an evolutionary novelty of the gnathostome ear. The existing general module mediating vertical canal growth and morphogenesis was modified by two sets of new genes: one set responsible for horizontal canal morphogenesis and another

  10. Autophagy is essential for cardiac morphogenesis during vertebrate development.

    PubMed

    Lee, Eunmyong; Koo, Yeon; Ng, Aylwin; Wei, Yongjie; Luby-Phelps, Kate; Juraszek, Amy; Xavier, Ramnik J; Cleaver, Ondine; Levine, Beth; Amatruda, James F

    2014-04-01

    Genetic analyses indicate that autophagy, an evolutionarily conserved lysosomal degradation pathway, is essential for eukaryotic differentiation and development. However, little is known about whether autophagy contributes to morphogenesis during embryogenesis. To address this question, we examined the role of autophagy in the early development of zebrafish, a model organism for studying vertebrate tissue and organ morphogenesis. Using zebrafish that transgenically express the fluorescent autophagy reporter protein, GFP-LC3, we found that autophagy is active in multiple tissues, including the heart, during the embryonic period. Inhibition of autophagy by morpholino knockdown of essential autophagy genes (including atg5, atg7, and becn1) resulted in defects in morphogenesis, increased numbers of dead cells, abnormal heart structure, and reduced organismal survival. Further analyses of cardiac development in autophagy-deficient zebrafish revealed defects in cardiac looping, abnormal chamber morphology, aberrant valve development, and ectopic expression of critical transcription factors including foxn4, tbx5, and tbx2. Consistent with these results, Atg5-deficient mice displayed abnormal Tbx2 expression and defects in valve development and chamber septation. Thus, autophagy plays an essential, conserved role in cardiac morphogenesis during vertebrate development.

  11. Morphogenesis and evolution of vertebrate appendicular muscle

    PubMed Central

    HAINES, LYNN; CURRIE, PETER D.

    2001-01-01

    Two different modes are utilised by vertebrate species to generate the appendicular muscle present within fins and limbs. Primitive Chondricthyan or cartilaginous fishes use a primitive mode of muscle formation to generate the muscle of the fins. Direct epithelial myotomal extensions invade the fin and generate the fin muscles while remaining in contact with the myotome. Embryos of amniotes such as chick and mouse use a similar mechanism to that deployed in the bony teleost species, zebrafish. Migratory mesenchymal myoblasts delaminate from fin/limb level somites, migrate to the fin/limb field and differentiate entirely within the context of the fin/limb bud. Migratory fin and limb myoblasts express identical genes suggesting that they possess both morphogenetic and molecular identity. We conclude that the mechanisms controlling tetrapod limb muscle formation arose prior to the Sarcopterygian or tetrapod radiation. PMID:11523824

  12. Morphogenesis and evolution of vertebrate appendicular muscle.

    PubMed

    Haines, L; Currie, P D

    2001-01-01

    Two different modes are utilised by vertebrate species to generate the appendicular muscle present within fins and limbs. Primitive Chondricthyan or cartilaginous fishes use a primitive mode of muscle formation to generate the muscle of the fins. Direct epithelial myotomal extensions invade the fin and generate the fin muscles while remaining in contact with the myotome. Embryos of amniotes such as chick and mouse use a similar mechanism to that deployed in the bony teleost species, zebrafish. Migratory mesenchymal myoblasts delaminate from fin/limb level somites, migrate to the fin/limb field and differentiate entirely within the context of the fin/limb bud. Migratory fin and limb myoblasts express identical genes suggesting that they possess both morphogenetic and molecular identity. We conclude that the mechanisms controlling tetrapod limb muscle formation arose prior to the Sarcopterygian or tetrapod radiation. PMID:11523824

  13. Anterior-posterior regionalized gene expression in the Ciona notochord

    PubMed Central

    Veeman, Michael

    2014-01-01

    Background In the simple ascidian chordate Ciona the signaling pathways and gene regulatory networks giving rise to initial notochord induction are largely understood and the mechanisms of notochord morphogenesis are being systematically elucidated. The notochord has generally been thought of as a non-compartmentalized or regionalized organ that is not finely patterned at the level of gene expression. Quantitative imaging methods have recently shown, however, that notochord cell size, shape and behavior vary consistently along the anterior-posterior (AP) axis. Results Here we screen candidate genes by whole mount in situ hybridization for potential AP asymmetry. We identify 4 genes that show non-uniform expression in the notochord. Ezrin/radixin/moesin (ERM) is expressed more strongly in the secondary notochord lineage than the primary. CTGF is expressed stochastically in a subset of notochord cells. A novel calmodulin-like gene (BCamL) is expressed more strongly at both the anterior and posterior tips of the notochord. A TGF-β ortholog is expressed in a gradient from posterior to anterior. The asymmetries in ERM, BCamL and TGF-β expression are evident even before the notochord cells have intercalated into a single-file column. Conclusions We conclude that the Ciona notochord is not a homogeneous tissue but instead shows distinct patterns of regionalized gene expression. PMID:24288133

  14. HNK-1 immunoreactivity during early morphogenesis of the head region in a nonmodel vertebrate, crocodile embryo

    NASA Astrophysics Data System (ADS)

    Kundrát, Martin

    2008-11-01

    The present study examines HNK-1 immunoidentification of a population of the neural crest (NC) during early head morphogenesis in the nonmodel vertebrate, the crocodile ( Crocodylus niloticus) embryos. Although HNK-1 is not an exclusive NC marker among vertebrates, temporospatial immunoreactive patterns found in the crocodile are almost consistent with NC patterns derived from gene expression studies known in birds (the closest living relatives of crocodiles) and mammals. In contrast to birds, the HNK-1 epitope is immunoreactive in NC cells at the neural fold level in crocodile embryos and therefore provides sufficient base to assess early migratory events of the cephalic NC. I found that crocodile NC forms three classic migratory pathways in the head: mandibular, hyoid, and branchial. Further, I demonstrate that, besides this classic phenotype, there is also a forebrain-derived migratory population, which consolidates into a premandibular stream in the crocodile. In contrast to the closely related chick model, crocodilian premandibular and mandibular NC cells arise from the open neural tube suggesting that species-specific heterochronic behavior of NC may be involved in the formation of different vertebrate facial phenotypes.

  15. Identifying Regulators of Morphogenesis Common to Vertebrate Neural Tube Closure and Caenorhabditis elegans Gastrulation.

    PubMed

    Sullivan-Brown, Jessica L; Tandon, Panna; Bird, Kim E; Dickinson, Daniel J; Tintori, Sophia C; Heppert, Jennifer K; Meserve, Joy H; Trogden, Kathryn P; Orlowski, Sara K; Conlon, Frank L; Goldstein, Bob

    2016-01-01

    Neural tube defects including spina bifida are common and severe congenital disorders. In mice, mutations in more than 200 genes can result in neural tube defects. We hypothesized that this large gene set might include genes whose homologs contribute to morphogenesis in diverse animals. To test this hypothesis, we screened a set of Caenorhabditis elegans homologs for roles in gastrulation, a topologically similar process to vertebrate neural tube closure. Both C. elegans gastrulation and vertebrate neural tube closure involve the internalization of surface cells, requiring tissue-specific gene regulation, actomyosin-driven apical constriction, and establishment and maintenance of adhesions between specific cells. Our screen identified several neural tube defect gene homologs that are required for gastrulation in C. elegans, including the transcription factor sptf-3. Disruption of sptf-3 in C. elegans reduced the expression of early endodermally expressed genes as well as genes expressed in other early cell lineages, establishing sptf-3 as a key contributor to multiple well-studied C. elegans cell fate specification pathways. We also identified members of the actin regulatory WAVE complex (wve-1, gex-2, gex-3, abi-1, and nuo-3a). Disruption of WAVE complex members reduced the narrowing of endodermal cells' apical surfaces. Although WAVE complex members are expressed broadly in C. elegans, we found that expression of a vertebrate WAVE complex member, nckap1, is enriched in the developing neural tube of Xenopus. We show that nckap1 contributes to neural tube closure in Xenopus. This work identifies in vivo roles for homologs of mammalian neural tube defect genes in two manipulable genetic model systems.

  16. FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation

    PubMed Central

    Libera, Laura; Boari, Nicola; Mortini, Pietro; Bellipanni, Gianfranco; Giordano, Antonio; Cotelli, Franco; Riva, Paola

    2014-01-01

    Chordoma is a rare malignant tumor that recapitulates the notochord phenotype and is thought to derive from notochord remnants not correctly regressed during development. Apoptosis is necessary for the proper notochord development in vertebrates, and the apoptotic pathway mediated by Fas and Fasl has been demonstrated to be involved in notochord cells regression. This study was conducted to investigate the expression of FAS/FASL pathway in a cohort of skull base chordomas and to analyze the role of fas/fasl homologs in zebrafish notochord formation. FAS/FASL expression was found to be dysregulated in chordoma leading to inactivation of the downstream Caspases in the samples analyzed. Both fas and fasl were specifically expressed in zebrafish notochord sorted cells. fas and fasl loss-of-function mainly resulted in larvae with notochord multi-cell-layer jumps organization, larger vacuolated notochord cells, defects in the peri-notochordal sheath structure and in vertebral mineralization. Interestingly, we observed the persistent expression of ntla and col2a1a, the zebrafish homologs of the human T gene and COL2A1 respectively, which are specifically up-regulated in chordoma. These results demonstrate for the first time the dysregulation of FAS/FASL in chordoma and their role in notochord formation in the zebrafish model, suggesting their possible implication in chordoma onset. PMID:25071022

  17. Antennas of organ morphogenesis: the roles of cilia in vertebrate kidney development.

    PubMed

    Marra, Amanda N; Li, Yue; Wingert, Rebecca A

    2016-09-01

    Cilia arose early during eukaryotic evolution, and their structural components are highly conserved from the simplest protists to complex metazoan species. In recent years, the role of cilia in the ontogeny of vertebrate organs has received increasing attention due to a staggering correlation between human disease and dysfunctional cilia. In particular, the presence of cilia in both the developing and mature kidney has become a deep area of research due to ciliopathies common to the kidney, such as polycystic kidney disease (PKD). Interestingly, mutations in genes encoding proteins that localize to the cilia cause similar cystic phenotypes in kidneys of various vertebrates, suggesting an essential role for cilia in kidney organogenesis and homeostasis as well. Importantly, the genes so far identified in kidney disease have conserved functions across species, whose kidneys include both primary and motile cilia. Here, we aim to provide a comprehensive description of cilia and their role in kidney development, as well as highlight the usefulness of the zebrafish embryonic kidney as a model to further understand the function of cilia in kidney health. PMID:27389733

  18. Antennas of organ morphogenesis: the roles of cilia in vertebrate kidney development

    PubMed Central

    Marra, Amanda N.; Li, Yue

    2016-01-01

    Abstract Cilia arose early during eukaryotic evolution, and their structural components are highly conserved from the simplest protists to complex metazoan species. In recent years, the role of cilia in the ontogeny of vertebrate organs has received increasing attention due to a staggering correlation between human disease and dysfunctional cilia. In particular, the presence of cilia in both the developing and mature kidney has become a deep area of research due to ciliopathies common to the kidney, such as polycystic kidney disease (PKD). Interestingly, mutations in genes encoding proteins that localize to the cilia cause similar cystic phenotypes in kidneys of various vertebrates, suggesting an essential role for cilia in kidney organogenesis and homeostasis as well. Importantly, the genes so far identified in kidney disease have conserved functions across species, whose kidneys include both primary and motile cilia. Here, we aim to provide a comprehensive description of cilia and their role in kidney development, as well as highlight the usefulness of the zebrafish embryonic kidney as a model to further understand the function of cilia in kidney health. PMID:27389733

  19. Antennas of organ morphogenesis: the roles of cilia in vertebrate kidney development.

    PubMed

    Marra, Amanda N; Li, Yue; Wingert, Rebecca A

    2016-09-01

    Cilia arose early during eukaryotic evolution, and their structural components are highly conserved from the simplest protists to complex metazoan species. In recent years, the role of cilia in the ontogeny of vertebrate organs has received increasing attention due to a staggering correlation between human disease and dysfunctional cilia. In particular, the presence of cilia in both the developing and mature kidney has become a deep area of research due to ciliopathies common to the kidney, such as polycystic kidney disease (PKD). Interestingly, mutations in genes encoding proteins that localize to the cilia cause similar cystic phenotypes in kidneys of various vertebrates, suggesting an essential role for cilia in kidney organogenesis and homeostasis as well. Importantly, the genes so far identified in kidney disease have conserved functions across species, whose kidneys include both primary and motile cilia. Here, we aim to provide a comprehensive description of cilia and their role in kidney development, as well as highlight the usefulness of the zebrafish embryonic kidney as a model to further understand the function of cilia in kidney health.

  20. Did the notochord evolve from an ancient axial muscle? The axochord hypothesis

    PubMed Central

    Brunet, Thibaut; Lauri, Antonella

    2015-01-01

    The origin of the notochord is one of the key remaining mysteries of our evolutionary ancestry. Here, we present a multi‐level comparison of the chordate notochord to the axochord, a paired axial muscle spanning the ventral midline of annelid worms and other invertebrates. At the cellular level, comparative molecular profiling in the marine annelids P. dumerilii and C. teleta reveals expression of similar, specific gene sets in presumptive axochordal and notochordal cells. These cells also occupy corresponding positions in a conserved anatomical topology and undergo similar morphogenetic movements. At the organ level, a detailed comparison of bilaterian musculatures reveals that most phyla form axochord‐like muscles, suggesting that such a muscle was already present in urbilaterian ancestors. Integrating comparative evidence at the cell and organ level, we propose that the notochord evolved by modification of a ventromedian muscle followed by the assembly of an axial complex supporting swimming in vertebrate ancestors. PMID:26172338

  1. Apoptosis regulates notochord development in Xenopus

    PubMed Central

    Malikova, Marina; Van Stry, Melanie

    2009-01-01

    The notochord is the defining characteristic of the chordate embryo, and plays critical roles as a signaling center and as the primitive skeleton. In this study we show that early notochord development in Xenopus embryos is regulated by apoptosis. We find apoptotic cells in the notochord beginning at the neural groove stage and increasing in number as the embryo develops. These dying cells are distributed in an anterior to posterior pattern that is correlated with notochord extension through vacuolization. In axial mesoderm explants, inhibition of this apoptosis causes the length of the notochord to approximately double compared to controls. In embryos however, inhibition of apoptosis decreases the length of the notochord and it is severely kinked. This kinking also spreads from the anterior with developmental stage such that by the tadpole stage, the notochord lacks any recognizable structure, although notochord markers are expressed in a normal temporal pattern. Extension of the somites and neural plate mirror that of the notochord in these embryos, and the somites are severely disorganized. These data indicate that apoptosis is required for normal notochord development during the formation of the anterior-posterior axis, and its role in this process is discussed. PMID:17920580

  2. How was the notochord born?

    PubMed

    Satoh, Nori; Tagawa, Kuni; Takahashi, Hiroki

    2012-01-01

    More than 550 million years ago, chordates originated from a common ancestor shared with nonchordate deuterostomes by developing a novel type of larva, the "tadpole larva." The notochord is the supporting organ of the larval tail and the most prominent feature of chordates; indeed, phylum Chordata is named after this organ. In this review, we discuss the molecular mechanisms involved in the formation of the notochord over the course of chordate evolution with a special emphasis on a member of T-box gene family, Brachyury. Comparison of the decoded genome of a unicellular choanoflagellate with the genomes of sponge and cnidarians suggests that T-box gene family arose at the time of the evolution of multicellular animals. Gastrulation is a morphogenetic movement that is essential for the formation of two- or three-germ-layered embryos. Brachyury is transiently expressed in the blastopore (bp) region, where it confers on cells the ability to undergo invagination. This process is involved in the formation of the archenteron in all metazoans. This is a "primary" function of Brachyury. During the evolution of chordates, Brachyury gained an additional expression domain at the dorsal midline region of the bp. In this new expression domain, Brachyury served its "secondary" function, recruiting another set of target genes to form a dorsal axial organ, notochord. The Wnt/β-catenin, BMP/Nodal, and FGF-signaling pathways are involved in the transcriptional activation of Brachyury. We discuss the molecular mechanisms of Brachyury secondary function in the context of the dorsal-ventral (D-V) inversion theory and the aboral-dorsalization hypothesis. Although the scope of this review requires some degree of oversimplification of Brachyury function, it is beneficial to facilitate studies on the notochord formation, a central evolutionary developmental biology problem in the history of metazoan evolution, pointed out first by Alexander Kowalevsky.

  3. Chemical genetics suggests a critical role for lysyl oxidase in zebrafish notochord morphogenesis† †Electronic supplementary information (ESI) available: Figure showing the of effect of 5 and 6 on the notochord and experimental details for compounds 2–6. See DOI: 10.1039/b613673g Click here for additional data file.

    PubMed Central

    Anderson, Carrie; Bartlett, Stephen J.; Gansner, John M.; Wilson, Duncan; He, Ling; Gitlin, Jonathan D.

    2007-01-01

    As a result of a chemical genetic screen for modulators of metalloprotease activity, we report that 2-mercaptopyridine-N-oxide induces a conspicuous undulating notochord defect in zebrafish embryos, a phenocopy of the leviathan mutant. The location of the chemically-induced wavy notochord correlated with the timing of application, thus defining a narrow chemical sensitivity window during segmentation stages. Microscopic observations revealed that notochord undulations appeared during the phase of notochord cell vacuolation and notochord elongation. Notochord cells become swollen as well as disorganized, while electron microscopy revealed disrupted organization of collagen fibrils in the surrounding sheath. We demonstrate by assay in zebrafish extracts that 2-mercaptopyridine-N-oxide inhibits lysyl oxidase. Thus, we provide insight into notochord morphogenesis and reveal novel compounds for lysyl oxidase inhibition. Taken together, these data underline the utility of small molecules for elucidating the dynamic mechanisms of early morphogenesis and provide a potential explanation for the recently established role of copper in zebrafish notochord formation. PMID:17216056

  4. Stepwise enforcement of the notochord and its intersection with the myoseptum: an evolutionary path leading to development of the vertebra?

    PubMed

    Grotmol, Sindre; Kryvi, Harald; Keynes, Roger; Krossøy, Christel; Nordvik, Kari; Totland, Geir K

    2006-09-01

    The notochord constitutes the main axial support during the embryonic and larval stages, and the arrangement of collagen fibrils within the notochord sheath is assumed to play a decisive role in determining its functional properties as a fibre-wound hydrostatic skeleton. We have found that during early ontogeny in Atlantic salmon stepwise changes occur in the configuration of the collagen fibre-winding of the notochord sheath. The sheath consists of a basal lamina, a layer of type II collagen, and an elastica externa that delimits the notochord; and these constituents are secreted in a specific order. Initially, the collagen fibrils are circumferentially arranged perpendicular to the longitudinal axis, and this specific spatial fibril configuration is maintained until hatching when the collagen becomes reorganized into distinct layers or lamellae. Within each lamella, fibrils are parallel to each other, forming helices around the longitudinal axis of the notochord, with a tangent angle of 75-80 degrees to the cranio-caudal axis. The helical geometry shifts between adjacent lamellae, forming enantiomorphous left- and right-handed coils, respectively, thus enforcing the sheath. The observed changes in the fibre-winding configuration may reflect adaptation of the notochord to functional demands related to stage in ontogeny. When the vertebral bodies initially form as chordacentra, the collagen lamellae of the sheath in the vertebral region are fixed by the deposition of minerals; in the intervertebral region, however, they represent a pre-adaptation providing torsional stability to the intervertebral joint. Hence, these modifications of the sheath transform the notochord per se into a functional vertebral column. The elastica externa, encasing the notochord, has serrated surfaces, connected inward to the type II collagen of the sheath, and outward to type I collagen of the mesenchymal connective tissue surrounding the notochord. In a similar manner, the collagen

  5. Notochord-Derived BMP Antagonists Inhibit Endothelial Cell Generation and Network Formation

    PubMed Central

    Bressan, Michael; Davis, Patricia; Timmer, John; Herzlinger, Doris; Mikawa, Takashi

    2009-01-01

    Embryonic blood vessel formation is initially mediated through the sequential differentiation, migration, and assembly of endothelial cells (ECs). While many molecular signals that promote vascular development have been identified, little is known about suppressors of this process. In higher vertebrates, including birds and mammals, the vascular network forms throughout the embryonic disk with the exception of a region along the midline. We have previously shown that the notochord is responsible for the generation and maintenance of the avascular midline and that BMP antagonists expressed by this embryonic tissue, including Noggin and Chordin, can mimic this inhibitory role. Here we report that the notochord suppresses the generation of ECs from the mesoderm both in vivo and in vitro. We also report that the notochord diminishes the ability of mature ECs to organize into a primitive plexus. Furthermore, Noggin mimics notochord-based inhibition by preventing mesodermal EC generation and mature EC network formation. These findings suggest that the mesoderm surrounding the midline is competent to give rise to ECs and to form blood vessels, but that notochord derived-BMP antagonists suppress EC differentiation and maturation processes leading to inhibition of midline vessel formation. PMID:19041859

  6. Functional Brachyury Binding Sites Establish a Temporal Read-out of Gene Expression in the Ciona Notochord

    PubMed Central

    Passamaneck, Yale J.; Gazdoiu, Stefan; José-Edwards, Diana S.; Kugler, Jamie E.; Oda-Ishii, Izumi; Imai, Janice H.; Nibu, Yutaka; Di Gregorio, Anna

    2013-01-01

    The appearance of the notochord represented a milestone in Deuterostome evolution. The notochord is necessary for the development of the chordate body plan and for the formation of the vertebral column and numerous organs. It is known that the transcription factor Brachyury is required for notochord formation in all chordates, and that it controls transcription of a large number of target genes. However, studies of the structure of the cis-regulatory modules (CRMs) through which this control is exerted are complicated in vertebrates by the genomic complexity and the pan-mesodermal expression territory of Brachyury. We used the ascidian Ciona, in which the single-copy Brachyury is notochord-specific and CRMs are easily identifiable, to carry out a systematic characterization of Brachyury-downstream notochord CRMs. We found that Ciona Brachyury (Ci-Bra) controls most of its targets directly, through non-palindromic binding sites that function either synergistically or individually to activate early- and middle-onset genes, respectively, while late-onset target CRMs are controlled indirectly, via transcriptional intermediaries. These results illustrate how a transcriptional regulator can efficiently shape a shallow gene regulatory network into a multi-tiered transcriptional output, and provide insights into the mechanisms that establish temporal read-outs of gene expression in a fast-developing chordate embryo. PMID:24204212

  7. Collagen II Is Essential for the Removal of the Notochord and the Formation of Intervertebral Discs

    PubMed Central

    Aszódi, Attila; Chan, Danny; Hunziker, Ernst; Bateman, John F.; Fässler, Reinhard

    1998-01-01

    Collagen II is a fibril-forming collagen that is mainly expressed in cartilage. Collagen II–deficient mice produce structurally abnormal cartilage that lacks growth plates in long bones, and as a result these mice develop a skeleton without endochondral bone formation. Here, we report that Col2a1-null mice are unable to dismantle the notochord. This defect is associated with the inability to develop intervertebral discs (IVDs). During normal embryogenesis, the nucleus pulposus of future IVDs forms from regional expansion of the notochord, which is simultaneously dismantled in the region of the developing vertebral bodies. However, in Col2a1-null mice, the notochord is not removed in the vertebral bodies and persists as a rod-like structure until birth. It has been suggested that this regional notochordal degeneration results from changes in cell death and proliferation. Our experiments with wild-type mice showed that differential proliferation and apoptosis play no role in notochordal reorganization. An alternative hypothesis is that the cartilage matrix exerts mechanical forces that induce notochord removal. Several of our findings support this hypothesis. Immunohistological analyses, in situ hybridization, and biochemical analyses demonstrate that collagens I and III are ectopically expressed in Col2a1-null cartilage. Assembly of the abnormal collagens into a mature insoluble matrix is retarded and collagen fibrils are sparse, disorganized, and irregular. We propose that this disorganized abnormal cartilage collagen matrix is structurally weakened and is unable to constrain proteoglycan-induced osmotic swelling pressure. The accumulation of fluid leads to tissue enlargement and a reduction in the internal swelling pressure. These changes may be responsible for the abnormal notochord removal in Col2a1-null mice. Our studies also show that chondrocytes do not need a collagen II environment to express cartilage-specific matrix components and to hypertrophy

  8. Essential role of lysyl oxidases in notochord development

    PubMed Central

    Gansner, John M.; Mendelsohn, Bryce A.; Hultman, Keith A.; Johnson, Stephen L.; Gitlin, Jonathan D.

    2007-01-01

    Recent studies reveal a critical role for copper in the development of the zebrafish notochord, suggesting that specific cuproenzymes are required for the structural integrity of the notochord sheath. We now demonstrate that β-aminopropionitrile, a known inhibitor of the copper-dependent lysyl oxidases, causes notochord distortion in the zebrafish embryo identical to that seen in copper deficiency. Characterization of the zebrafish lysyl oxidase genes reveals eight unique sequences, several of which are expressed in the developing notochord. Specific gene knockdown demonstrates that loss of loxl1 results in notochord distortion, and that loxl1 and loxl5b have overlapping roles in notochord formation. Interestingly, while notochord abnormalities are not observed following partial knockdown of loxl1 or loxl5b alone, in each case this markedly sensitizes developing embryos to notochord distortion if copper availability is diminished. Likewise, partial knockdown of the lysyl oxidase substrate col2a1 results in notochord distortion when combined with reduced copper availability or partial knockdown of loxl1 or loxl5b. These data reveal a complex interplay of gene expression and nutrient availability critical to notochord development. They also provide insight into specific genetic and nutritional factors that may play a role in the pathogenesis of structural birth defects of the axial skeleton. PMID:17543297

  9. ngs (notochord granular surface) gene encodes a novel type of intermediate filament family protein essential for notochord maintenance in zebrafish.

    PubMed

    Tong, Xiangjun; Xia, Zhidan; Zu, Yao; Telfer, Helena; Hu, Jing; Yu, Jingyi; Liu, Huan; Zhang, Quan; Sodmergen; Lin, Shuo; Zhang, Bo

    2013-01-25

    The notochord is an important organ involved in embryonic patterning and locomotion. In zebrafish, the mature notochord consists of a single stack of fully differentiated, large vacuolated cells called chordocytes, surrounded by a single layer of less differentiated notochordal epithelial cells called chordoblasts. Through genetic analysis of zebrafish lines carrying pseudo-typed retroviral insertions, a mutant exhibiting a defective notochord with a granular appearance was isolated, and the corresponding gene was identified as ngs (notochord granular surface), which was specifically expressed in the notochord. In the mutants, the notochord started to degenerate from 32 hours post-fertilization, and the chordocytes were then gradually replaced by smaller cells derived from chordoblasts. The granular notochord phenotype was alleviated by anesthetizing the mutant embryos with tricaine to prevent muscle contraction and locomotion. Phylogenetic analysis showed that ngs encodes a new type of intermediate filament (IF) family protein, which we named chordostatin based on its function. Under the transmission electron microcopy, bundles of 10-nm-thick IF-like filaments were enriched in the chordocytes of wild-type zebrafish embryos, whereas the chordocytes in ngs mutants lacked IF-like structures. Furthermore, chordostatin-enhanced GFP (EGFP) fusion protein assembled into a filamentous network specifically in chordocytes. Taken together, our work demonstrates that ngs encodes a novel type of IF protein and functions to maintain notochord integrity for larval development and locomotion. Our work sheds light on the mechanisms of notochord structural maintenance, as well as the evolution and biological function of IF family proteins.

  10. Molecular analysis of axon repulsion by the notochord.

    PubMed

    Anderson, Christopher N G; Ohta, Kunimasa; Quick, Marie M; Fleming, Angeleen; Keynes, Roger; Tannahill, David

    2003-03-01

    During development of the amniote peripheral nervous system, the initial trajectory of primary sensory axons is determined largely by the action of axon repellents. We have shown previously that tissues flanking dorsal root ganglia, the notochord lying medially and the dermamyotomes lying laterally, are sources of secreted molecules that prevent axons from entering inappropriate territories. Although there is evidence suggesting that SEMA3A contributes to the repellent activity of the dermamyotome, the nature of the activity secreted by the notochord remains undetermined. We have employed an expression cloning strategy to search for axon repellents secreted by the notochord, and have identified SEMA3A as a candidate repellent. Moreover, using a spectrum of different axon populations to assay the notochord activity, together with neuropilin/Fc receptor reagents to block semaphorin activity in collagen gel assays, we show that SEMA3A probably contributes to notochord-mediated repulsion. Sympathetic axons that normally avoid the midline in vivo are also repelled, in part, by a semaphorin-based notochord activity. Although our results implicate semaphorin signalling in mediating repulsion by the notochord, repulsion of early dorsal root ganglion axons is only partially blocked when using neuropilin/Fc reagents. Moreover, retinal axons, which are insensitive to SEMA3A, are also repelled by the notochord. We conclude that multiple factors act in concert to guide axons in this system, and that further notochord repellents remain to be identified.

  11. Developing pressures: fluid forces driving morphogenesis

    PubMed Central

    Navis, Adam; Bagnat, Michel

    2015-01-01

    Over several decades genetic studies have unraveled many molecular mechanisms that underlie the signaling networks guiding morphogenesis, but the mechanical forces at work remain much less well understood. Accumulation of fluid within a luminal space can generate outward hydrostatic pressure capable of shaping morphogenesis at several scales, ranging from individual organs to the entire vertebrate body-plan. Here, we focus on recent work that uncovered mechanical roles for fluid secretion during morphogenesis. Identifying the roles and regulation of fluid secretion will be instrumental for understanding the mechanics of morphogenesis as well as many human diseases of complex genetic and environmental origin including secretory diarrheas and scoliosis. PMID:25698116

  12. Cytomorphologic findings of intraosseous notochordal rest on touch preparation: a case report.

    PubMed

    Bovbel, Alexandra; Zaheer, Atif; Maleki, Zahra

    2015-03-01

    Intraosseous notochordal rest is a rare intravertebral lesion of notochord origin which is presumably benign. It is usually an incidental finding in microscopic examination of vertebrectomy due to unrelated lesions or autopsy cases. Chordoma is a malignant neoplasm originating from notochord with a different clinicoradiographic presentation, prognosis, and treatment. However, the histology of intraosseous notochordal rest and chordoma is almost identical. Herein, we report cytomorphologic findings of a case of intraossous notochordal rest on touch preparation.

  13. Vertebral Development in Paleozoic and Mesozoic Tetrapods Revealed by Paleohistological Data

    PubMed Central

    Danto, Marylène; Witzmann, Florian; Fröbisch, Nadia B.

    2016-01-01

    Basal tetrapods display a wide spectrum of vertebral centrum morphologies that can be used to distinguish different tetrapod groups. The vertebral types range from multipartite centra in stem-tetrapods, temnospondyls, and seymouriamorphs up to monospondylous centra in lepospondyls and have been drawn upon for reconstructing major evolutionary trends in tetrapods that are now considered textbook knowledge. Two modes of vertebral formation have been postulated: the multipartite vertebrae formed first as cartilaginous elements with subsequent ossification. The monospondylous centrum, in contrast, was formed by direct ossification without a cartilaginous precursor. This study describes centrum morphogenesis in basal tetrapods for the first time, based on bone histology. Our results show that the intercentra of the investigated stem-tetrapods consist of a small band of periosteal bone and a dense network of endochondral bone. In stereospondyl temnospondyls, high amounts of calcified cartilage are preserved in the endochondral trabeculae. Notably, the periosteal region is thickened and highly vascularized in the plagiosaurid stereospondyls. Among “microsaur” lepospondyls, the thickened periosteal region is composed of compact bone and the notochordal canal is surrounded by large cell lacunae. In nectridean lepospondyls, the periosteal region has a spongy structure with large intertrabecular spaces, whereas the endochondral region has a highly cancellous structure. Our observations indicate that regardless of whether multipartite or monospondylous, the centra of basal tetrapods display first endochondral and subsequently periosteal ossification. A high interspecific variability is observed in growth rate, organization, and initiation of periosteal ossification. Moreover, vertebral development and structure reflect different lifestyles. The bottom-dwelling Plagiosauridae increase their skeletal mass by hyperplasy of the periosteal region. In nectrideans, the skeletal

  14. Building the backbone: the development and evolution of vertebral patterning.

    PubMed

    Fleming, Angeleen; Kishida, Marcia G; Kimmel, Charles B; Keynes, Roger J

    2015-05-15

    The segmented vertebral column comprises a repeat series of vertebrae, each consisting of two key components: the vertebral body (or centrum) and the vertebral arches. Despite being a defining feature of the vertebrates, much remains to be understood about vertebral development and evolution. Particular controversy surrounds whether vertebral component structures are homologous across vertebrates, how somite and vertebral patterning are connected, and the developmental origin of vertebral bone-mineralizing cells. Here, we assemble evidence from ichthyologists, palaeontologists and developmental biologists to consider these issues. Vertebral arch elements were present in early stem vertebrates, whereas centra arose later. We argue that centra are homologous among jawed vertebrates, and review evidence in teleosts that the notochord plays an instructive role in segmental patterning, alongside the somites, and contributes to mineralization. By clarifying the evolutionary relationship between centra and arches, and their varying modes of skeletal mineralization, we can better appreciate the detailed mechanisms that regulate and diversify vertebral patterning.

  15. Building the backbone: the development and evolution of vertebral patterning.

    PubMed

    Fleming, Angeleen; Kishida, Marcia G; Kimmel, Charles B; Keynes, Roger J

    2015-05-15

    The segmented vertebral column comprises a repeat series of vertebrae, each consisting of two key components: the vertebral body (or centrum) and the vertebral arches. Despite being a defining feature of the vertebrates, much remains to be understood about vertebral development and evolution. Particular controversy surrounds whether vertebral component structures are homologous across vertebrates, how somite and vertebral patterning are connected, and the developmental origin of vertebral bone-mineralizing cells. Here, we assemble evidence from ichthyologists, palaeontologists and developmental biologists to consider these issues. Vertebral arch elements were present in early stem vertebrates, whereas centra arose later. We argue that centra are homologous among jawed vertebrates, and review evidence in teleosts that the notochord plays an instructive role in segmental patterning, alongside the somites, and contributes to mineralization. By clarifying the evolutionary relationship between centra and arches, and their varying modes of skeletal mineralization, we can better appreciate the detailed mechanisms that regulate and diversify vertebral patterning. PMID:25968309

  16. Extraosseous Benign Notochordal Cell Tumor Originating in the Lung

    PubMed Central

    Takahashi, Yusuke; Motoi, Toru; Harada, Masahiko; Fukuda, Yumiko; Hishima, Tsunekazu; Horio, Hirotoshi

    2015-01-01

    Abstract Benign notochordal cell tumors (BNCTs) are tumors originating in the axial skeleton, where chordomas occur. Although very rare, some cases of extraosseous chordoma, such as in the soft tissue and lungs, have been reported. We report a case of a primary tumor showing the notochordal characteristics of BNCTs within the axial skeleton. An asymptomatic 57-year-old woman presented with an abnormal shadow on her chest radiograph; chest computed tomography revealed a well-defined round nodule. The resected sample tissue contained a jelly-like small nodule. Histologically, it was identified as a BNCT, based on minimal nuclear atypia, extremely low mitotic activity within the tumor cells lying in a sheet-like arrangement, and focal immunopositivity for brachyury. This is the third case report of BNCT originating in the lungs; BNCTs are considered asymptomatic tumors that are identified by using highly developed chest imaging technology; however, our findings also suggest that these notochordal tumors may potentially originate from extraosseous sites that lack ideal precursor cells. Our case suggests that notochordal tumors can arise from organs that are unrelated to known notochordal development. PMID:25569657

  17. The generation of vertebral segmental patterning in the chick embryo.

    PubMed

    Senthinathan, Biruntha; Sousa, Cátia; Tannahill, David; Keynes, Roger

    2012-06-01

    We have carried out a series of experimental manipulations in the chick embryo to assess whether the notochord, neural tube and spinal nerves influence segmental patterning of the vertebral column. Using Pax1 expression in the somite-derived sclerotomes as a marker for segmentation of the developing intervertebral disc, our results exclude such an influence. In contrast to certain teleost species, where the notochord has been shown to generate segmentation of the vertebral bodies (chordacentra), these experiments indicate that segmental patterning of the avian vertebral column arises autonomously in the somite mesoderm. We suggest that in amniotes, the subdivision of each sclerotome into non-miscible anterior and posterior halves plays a critical role in establishing vertebral segmentation, and in maintaining left/right alignment of the developing vertebral elements at the body midline.

  18. Loss of col8a1a function during zebrafish embryogenesis results in congenital vertebral malformations.

    PubMed

    Gray, Ryan S; Wilm, Thomas P; Smith, Jeff; Bagnat, Michel; Dale, Rodney M; Topczewski, Jacek; Johnson, Stephen L; Solnica-Krezel, Lilianna

    2014-02-01

    Congenital vertebral malformations (CVM) occur in 1 in 1000 live births and in many cases can cause spinal deformities, such as scoliosis, and result in disability and distress of affected individuals. Many severe forms of the disease, such as spondylocostal dystostosis, are recessive monogenic traits affecting somitogenesis, however the etiologies of the majority of CVM cases remain undetermined. Here we demonstrate that morphological defects of the notochord in zebrafish can generate congenital-type spine defects. We characterize three recessive zebrafish leviathan/col8a1a mutant alleles ((m531, vu41, vu105)) that disrupt collagen type VIII alpha1a (col8a1a), and cause folding of the embryonic notochord and consequently adult vertebral column malformations. Furthermore, we provide evidence that a transient loss of col8a1a function or inhibition of Lysyl oxidases with drugs during embryogenesis was sufficient to generate vertebral fusions and scoliosis in the adult spine. Using periodic imaging of individual zebrafish, we correlate focal notochord defects of the embryo with vertebral malformations (VM) in the adult. Finally, we show that bends and kinks in the notochord can lead to aberrant apposition of osteoblasts normally confined to well-segmented areas of the developing vertebral bodies. Our results afford a novel mechanism for the formation of VM, independent of defects of somitogenesis, resulting from aberrant bone deposition at regions of misshapen notochord tissue.

  19. Loss of col8a1a Function during Zebrafish Embryogenesis Results in Congenital Vertebral Malformations

    PubMed Central

    Gray, Ryan S.; Wilm, Thomas; Smith, Jeff; Bagnat, Michel; Dale, Rodney M.; Topczewski, Jacek; Johnson, Stephen L.; Solnica-Krezel, Lilianna

    2014-01-01

    Congenital vertebral malformations (CVM) occur in 1 in 1,000 live births and in many cases can cause spinal deformities, such as scoliosis, and result in disability and distress of affected individuals. Many severe forms of the disease, such as spondylocostal dystostosis, are recessive monogenic traits affecting somitogenesis, however the etiologies of the majority of CVM cases remain undetermined. Here we demonstrate that morphological defects of the notochord in zebrafish can generate congenital-type spine defects. We characterize three recessive zebrafish leviathan/col8a1a mutant alleles (m531, vu41, vu105) that disrupt collagen type VIII alpha1a (col8a1a), and cause folding of the embryonic notochord and consequently adult vertebral column malformations. Furthermore, we provide evidence that a transient loss of col8a1a function or inhibition of Lysyl oxidases with drugs during embryogenesis was sufficient to generate vertebral fusions and scoliosis in the adult spine. Using periodic imaging of individual zebrafish, we correlate focal notochord defects of the embryo with vertebral malformations (VM) in the adult. Finally, we show that bends and kinks in the notochord can lead to aberrant apposition of osteoblasts normally confined to well-segmented areas of the developing vertebral bodies. Our results afford a novel mechanism for the formation of VM, independent of defects of somitogenesis, resulting from aberrant bone deposition at regions of misshapen notochord tissue. PMID:24333517

  20. Activity and Distribution of Paxillin, Focal Adhesion Kinase, and Cadherin Indicate Cooperative Roles during Zebrafish Morphogenesis

    PubMed Central

    Crawford, Bryan D.; Henry, Clarissa A.; Clason, Todd A.; Becker, Amanda L.; Hille, Merrill B.

    2003-01-01

    We investigated the focal adhesion proteins paxillin and Fak, and the cell-cell adhesion protein cadherin in developing zebrafish (Danio rerio) embryos. Cadherins are expressed in presomitic mesoderm where they delineate cells. The initiation of somite formation coincides with an increase in the phosphorylation of Fak, and the accumulation of Fak, phosphorylated Fak, paxillin, and fibronectin at nascent somite boundaries. In the notochord, cadherins are expressed on cells during intercalation, and phosphorylated Fak accumulates in circumferential rings where the notochord cells contact laminin in the perichordal sheath. Subsequently, changes in the orientations of collagen fibers in the sheath suggest that Fak-mediated adhesion allows longitudinal expansion of the notochord, but not lateral expansion, resulting in notochord elongation. Novel observations showed that focal adhesion kinase and paxillin concentrate at sites of cell-cell adhesion in the epithelial enveloping layer and may associate with actin cytoskeleton at epithelial junctions containing cadherins. Fak is phosphorylated at these epithelial junctions but is not phosphorylated on Tyr397, implicating a noncanonical mechanism of regulation. These data suggest that Fak and paxillin may function in the integration of cadherin-based and integrin-based cell adhesion during the morphogenesis of the early zebrafish embryo. PMID:12925747

  1. Notochord Cells in Intervertebral Disc Development and Degeneration

    PubMed Central

    McCann, Matthew R.; Séguin, Cheryle A.

    2016-01-01

    The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

  2. Coordinated activation of the secretory pathway during notochord formation in the Xenopus embryo

    PubMed Central

    Tanegashima, Kosuke; Zhao, Hui; Rebbert, Martha L.; Dawid, Igor B.

    2009-01-01

    Summary We compared the transcriptome in the developing notochord of Xenopus laevis embryos with that of other embryonic regions. A coordinated and intense activation of a large set of secretory pathway genes was observed in the notochord, but not in notochord precursors in the axial mesoderm at early gastrula stage. The genes encoding Xbp1 and Creb3l2 were also activated in the notochord. These two transcription factors are implicated in the activation of secretory pathway genes during the unfolded protein response, where cells react to the stress of a build-up of unfolded proteins in their endoplasmic reticulum. Xbp1 and Creb3l2 are differentially expressed but not differentially activated in the notochord. Reduction of expression of Xbp1 or Creb3l2 by injection of antisense morpholinos led to strong deficits in notochord but not somitic muscle development. In addition, the expression of some, but not all, genes encoding secretory proteins was inhibited by injection of xbp1 morpholinos. Furthermore, expression of activated forms of Xbp1 or Creb3l2 in animal explants could activate a similar subset of secretory pathway genes. We conclude that coordinated activation of a battery of secretory pathway genes mediated by Xbp1 and Creb/ATF factors is a characteristic and necessary feature of notochord formation. PMID:19793890

  3. Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord.

    PubMed

    José-Edwards, Diana S; Oda-Ishii, Izumi; Kugler, Jamie E; Passamaneck, Yale J; Katikala, Lavanya; Nibu, Yutaka; Di Gregorio, Anna

    2015-12-01

    A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs. PMID:26684323

  4. Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord

    PubMed Central

    José-Edwards, Diana S.; Oda-Ishii, Izumi; Kugler, Jamie E.; Passamaneck, Yale J.; Katikala, Lavanya; Nibu, Yutaka; Di Gregorio, Anna

    2015-01-01

    A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs. PMID:26684323

  5. FoxA4 Favours Notochord Formation by Inhibiting Contiguous Mesodermal Fates and Restricts Anterior Neural Development in Xenopus Embryos

    PubMed Central

    Murgan, Sabrina; Castro Colabianchi, Aitana Manuela; Monti, Renato José; Boyadjián López, Laura Elena; Aguirre, Cecilia E.; Stivala, Ernesto González; López, Silvia L.

    2014-01-01

    In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula –chordin and –noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development. PMID:25343614

  6. An amphioxus winged helix/forkhead gene, AmphiFoxD: insights into vertebrate neural crest evolution

    NASA Technical Reports Server (NTRS)

    Yu, Jr-Kai; Holland, Nicholas D.; Holland, Linda Z.

    2002-01-01

    During amphioxus development, the neural plate is bordered by cells expressing many genes with homologs involved in vertebrate neural crest induction. However, these amphioxus cells evidently lack additional genetic programs for the cell delaminations, migrations, and differentiations characterizing definitive vertebrate neural crest. We characterize an amphioxus winged helix/forkhead gene (AmphiFoxD) closely related to vertebrate FoxD genes. Phylogenetic analysis indicates that the AmphiFoxD is basal to vertebrate FoxD1, FoxD2, FoxD3, FoxD4, and FoxD5. One of these vertebrate genes (FoxD3) consistently marks neural crest during development. Early in amphioxus development, AmphiFoxD is expressed medially in the anterior neural plate as well as in axial (notochordal) and paraxial mesoderm; later, the gene is expressed in the somites, notochord, cerebral vesicle (diencephalon), and hindgut endoderm. However, there is never any expression in cells bordering the neural plate. We speculate that an AmphiFoxD homolog in the common ancestor of amphioxus and vertebrates was involved in histogenic processes in the mesoderm (evagination and delamination of the somites and notochord); then, in the early vertebrates, descendant paralogs of this gene began functioning in the presumptive neural crest bordering the neural plate to help make possible the delaminations and cell migrations that characterize definitive vertebrate neural crest. Copyright 2002 Wiley-Liss, Inc.

  7. Trichome morphogenesis in Arabidopsis.

    PubMed Central

    Schwab, B; Folkers, U; Ilgenfritz, H; Hülskamp, M

    2000-01-01

    Trichomes (plant hairs) in Arabidopsis thaliana are large non-secreting epidermal cells with a characteristic three-dimensional architecture. Because trichomes are easily accessible to a combination of genetic, cell biological and molecular methods they have become an ideal model system to study various aspects of plant cell morphogenesis. In this review we will summarize recent progress in the understanding of trichome morphogenesis. PMID:11128981

  8. Dynamics of cell polarity in tissue morphogenesis: a comparative view from Drosophila and Ciona.

    PubMed

    Veeman, Michael T; McDonald, Jocelyn A

    2016-01-01

    Tissues in developing embryos exhibit complex and dynamic rearrangements that shape forming organs, limbs, and body axes. Directed migration, mediolateral intercalation, lumen formation, and other rearrangements influence the topology and topography of developing tissues. These collective cell behaviors are distinct phenomena but all involve the fine-grained control of cell polarity. Here we review recent findings in the dynamics of polarized cell behavior in both the Drosophila ovarian border cells and the Ciona notochord. These studies reveal the remarkable reorganization of cell polarity during organ formation and underscore conserved mechanisms of developmental cell polarity including the Par/atypical protein kinase C (aPKC) and planar cell polarity pathways. These two very different model systems demonstrate important commonalities but also key differences in how cell polarity is controlled in tissue morphogenesis. Together, these systems raise important, broader questions on how the developmental control of cell polarity contributes to morphogenesis of diverse tissues across the metazoa.

  9. Dynamics of cell polarity in tissue morphogenesis: a comparative view from Drosophila and Ciona

    PubMed Central

    Veeman, Michael T.; McDonald, Jocelyn A.

    2016-01-01

    Tissues in developing embryos exhibit complex and dynamic rearrangements that shape forming organs, limbs, and body axes. Directed migration, mediolateral intercalation, lumen formation, and other rearrangements influence the topology and topography of developing tissues. These collective cell behaviors are distinct phenomena but all involve the fine-grained control of cell polarity. Here we review recent findings in the dynamics of polarized cell behavior in both the Drosophila ovarian border cells and the Ciona notochord. These studies reveal the remarkable reorganization of cell polarity during organ formation and underscore conserved mechanisms of developmental cell polarity including the Par/atypical protein kinase C (aPKC) and planar cell polarity pathways. These two very different model systems demonstrate important commonalities but also key differences in how cell polarity is controlled in tissue morphogenesis. Together, these systems raise important, broader questions on how the developmental control of cell polarity contributes to morphogenesis of diverse tissues across the metazoa. PMID:27303647

  10. Vertebral development and amphibian evolution.

    PubMed

    Carroll, R L; Kuntz, A; Albright, K

    1999-01-01

    Amphibians provide an unparalleled opportunity to integrate studies of development and evolution through the investigation of the fossil record of larval stages. The pattern of vertebral development in modern frogs strongly resembles that of Paleozoic labyrinthodonts in the great delay in the ossification of the vertebrae, with the centra forming much later than the neural arches. Slow ossification of the trunk vertebrae in frogs and the absence of ossification in the tail facilitate the rapid loss of the tail during metamorphosis, and may reflect retention of the pattern in their specific Paleozoic ancestors. Salamanders and caecilians ossify their centra at a much earlier stage than frogs, which resembles the condition in Paleozoic lepospondyls. The clearly distinct patterns and rates of vertebral development may indicate phylogenetic separation between the ultimate ancestors of frogs and those of salamanders and caecilians within the early radiation of ancestral tetrapods. This divergence may date from the Lower Carboniferous. Comparison with the molecular regulation of vertebral development described in modern mammals and birds suggests that the rapid chondrification of the centra in salamanders relative to that of frogs may result from the earlier migration of sclerotomal cells expressing Pax1 to the area surrounding the notochord.

  11. Vertebral development and amphibian evolution.

    PubMed

    Carroll, R L; Kuntz, A; Albright, K

    1999-01-01

    Amphibians provide an unparalleled opportunity to integrate studies of development and evolution through the investigation of the fossil record of larval stages. The pattern of vertebral development in modern frogs strongly resembles that of Paleozoic labyrinthodonts in the great delay in the ossification of the vertebrae, with the centra forming much later than the neural arches. Slow ossification of the trunk vertebrae in frogs and the absence of ossification in the tail facilitate the rapid loss of the tail during metamorphosis, and may reflect retention of the pattern in their specific Paleozoic ancestors. Salamanders and caecilians ossify their centra at a much earlier stage than frogs, which resembles the condition in Paleozoic lepospondyls. The clearly distinct patterns and rates of vertebral development may indicate phylogenetic separation between the ultimate ancestors of frogs and those of salamanders and caecilians within the early radiation of ancestral tetrapods. This divergence may date from the Lower Carboniferous. Comparison with the molecular regulation of vertebral development described in modern mammals and birds suggests that the rapid chondrification of the centra in salamanders relative to that of frogs may result from the earlier migration of sclerotomal cells expressing Pax1 to the area surrounding the notochord. PMID:11324019

  12. Dynamic epithelia of the developing vertebrate face

    PubMed Central

    Choe, Chong Pyo; Crump, J. Gage

    2015-01-01

    A segmental series of endoderm-derived pouch and ectoderm-derived cleft epithelia act as signaling centers in the developing face. Their precise morphogenesis is therefore essential for proper patterning of the vertebrate head. Intercellular adhesion and polarity are highly dynamic within developing facial epithelial cells, with signaling from the adjacent mesenchyme controlling both epithelial character and directional migration. Endodermal and ectodermal epithelia fuse to form the primary mouth and gill slits, which involves basement membrane dissolution, cell intercalations, and apoptosis, as well as undergo further morphogenesis to generate the middle ear cavity and glands of the neck. Recent studies of facial epithelia are revealing both core programs of epithelial morphogenesis and insights into the coordinated assembly of the vertebrate head. PMID:25748249

  13. Muscular contractions in the zebrafish embryo are necessary to reveal thiuram-induced notochord distortions

    SciTech Connect

    Teraoka, Hiroki . E-mail: hteraoka@rakuno.ac.jp; Urakawa, Satsuki; Nanba, Satomi; Nagai, Yuhki; Wu Dong; Imagawa, Tomohiro; Tanguay, Robert L.; Svoboda, Kurt; Handley-Goldstone, Heather M.; Stegeman, John J.; Hiraga, Takeo

    2006-04-01

    Dithiocarbamates form a large group of chemicals that have numerous uses in agriculture and medicine. It has been reported that dithiocarbamates, including thiuram (tetramethylthiuram disulfide), cause wavy distortions of the notochord in zebrafish and other fish embryos. In the present study, we investigated the mechanism underlying the toxicity of thiuram in zebrafish embryos. When embryos were exposed to thiuram (2-1000 nM: 0.48-240 {mu}g/L) from 3 h post fertilization (hpf) (30% epiboly) until 24 hpf (Prim-5), all embryos develop wavy notochords, disorganized somites, and have shortened yolk sac extensions. The thiuram response was specific and did not cause growth retardation or mortality at 24 hpf. The thiuram-dependent responses showed the same concentration dependence with a waterborne EC{sub 5} values of approximately 7 nM. Morphometric measurements revealed that thiuram does not affect the rate of notochord lengthening. However, the rate of overall body lengthening was significantly reduced in thiuram-exposed animals. Other dithiocarbamates, such as ziram, caused similar malformations to thiuram. While expression of genes involved in somitogenesis was not affected, the levels of notochord-specific transcripts were altered after the onset of malformations. Distortion of the notochord started precisely at 18 hpf, which is concomitant with onset of spontaneous rhythmic trunk contractions. Abolishment of spontaneous contractions using tricaine, {alpha}-bungarotoxin, and a paralytic mutant sofa potato, resulted in normal notochord morphology in the presence of thiuram. These results indicate that muscle activity is necessary to reveal the underlying functional deficit and suggest that the developmental target of dithiocarbamates impairs trunk plasticity through an unknown mechanism.

  14. Multicellular Models of Morphogenesis

    EPA Science Inventory

    EPA’s Virtual Embryo project (v-Embryo™), in collaboration with developers of CompuCell3D, aims to create computer models of morphogenesis that can be used to address the effects of chemical perturbation on embryo development at the cellular level. Such computational (in silico) ...

  15. The origin of the vertebrate skeleton

    NASA Astrophysics Data System (ADS)

    Pivar, Stuart

    2011-01-01

    The anatomy of the human and other vertebrates has been well described since the days of Leonardo da Vinci and Vesalius. The causative origin of the configuration of the bones and of their shapes and forms has been addressed over the ensuing centuries by such outstanding investigators as Goethe, Von Baer, Gegenbauer, Wilhelm His and D'Arcy Thompson, who sought to apply mechanical principles to morphogenesis. However, no coherent causative model of morphogenesis has ever been presented. This paper presents a causative model for the origin of the vertebrate skeleton, based on the premise that the body is a mosaic enlargement of self-organized patterns engrained in the membrane of the egg cell. Drawings illustrate the proposed hypothetical origin of membrane patterning and the changes in the hydrostatic equilibrium of the cytoplasm that cause topographical deformations resulting in the vertebrate body form.

  16. TOWARDS AN UNDERSTANDING OF THE ROLE OF NOTOCHORDAL CELLS IN THE ADULT INTERVERTEBRAL DISC: FROM DISCORD TO ACCORD

    PubMed Central

    Risbud, Makarand V.; Schaer, Thomas P.; Shapiro, Irving M.

    2013-01-01

    The goal of this mini-review is to address the long standing argument that the pathogenesis of disc disease is due to the loss and/or the replacement of the notochordal cells by other cell types. We contend that although cells of different size and morphology exist, there is no strong evidence to support the view that the nucleus pulposus contains cells of distinct lineages. Based on lineage mapping studies and studies of other notochordal markers, we hypothesize that in all animals including human, nucleus pulposus retains notochordal cells throughout life. Moreover, all cells including chondrocyte-like cells are derived from notochordal precursors and that variations in morphology and size are representative of different stages of maturation, and or, function. Thus, the most critical choice for a suitable animal model should relate more to the anatomical, and mechanical characteristics of the motion segment than concerns of cell loss and replacement by non-notochordal cells. PMID:20568241

  17. A rare case of intraosseous benign notochordal cell tumor of the coccyx.

    PubMed

    Uglialoro, Anthony D; Beebe, Kathleen S; Hameed, Meera; Benevenia, Joseph

    2009-06-01

    This article presents a case of a 53-year-old woman who presented with intermittent, dull, poorly localized lower back and buttock pain. The pain worsened in a seated position or after long periods of standing. A T1-weighted magnetic resonance image (MRI) of the sacrum and coccyx revealed a well-demarcated intraosseous lesion with homogeneous low signal intensity, while T2-weighted MRIs demonstrated homogeneous high signal intensity. An excisional biopsy revealed benign notochord cell tumor. The biopsy proved to be effective, as it relieved the patient's coccydynia. Due to the rarity of intraosseous benign notochordal cell tumors, it is essential to document and review this type of tumor. Only 2 benign notochordal cell tumors involving the coccyx have been previously reported, both of which presented with the same clinical symptoms of chronic coccydynia as our patient, likely due to the location of the involved lesion. The other leading diagnosis in our patient was chordoma, a malignant and locally aggressive neoplasm that is important to consider and exclude. Although chordomas have been well characterized in the surgery, pathology, and radiology literature, the benign notochordal cell tumor is a relative newcomer.

  18. A case of split notochord syndrome: Presenting with respiratory failure in the neonatal period

    PubMed Central

    Coskun, Yesim; Akman, Ipek; Demir, Mustafa Kemal; Yapicier, Ozlem; Somuncu, Salih

    2016-01-01

    Summary Split notochord syndrome (SNS) is a very rare congenital anomaly. This report describes a male newborn with a neuroenteric cyst in the posterior mediastinum and multiple vertebrae anomalies presenting with respiratory failure and pulmonary hypertension. This report also discusses the embryological development and the etiologic theories of SNS. PMID:27195197

  19. The early origin of vertebral anomalies, as illustrated by a 'butterfly vertebra'.

    PubMed Central

    Müller, F; O'Rahilly, R; Benson, D R

    1986-01-01

    An anomalous (butterfly) eleventh thoracic vertebra in a fetus of 63 mm greatest length is described and graphic reconstructions (together with normal controls) are provided. The cartilaginous hemicentra are separated by disc-like material. Cartilaginous bars to adjacent vertebrae are present. The neural arch is complete. The notochord is not duplicated. Only one comparable case in the embryonic period has been described previously. After a discussion of cleft vertebrae in the human and in experimental animals, a developmental timetable of the appearance of several vertebral anomalies is provided. The sensitive period for butterfly vertebrae, depending on the mode of origin, seems to be 3-6 postovulatory weeks. More severe anomalies, such as the split notochord syndrome, appear earlier. It is concluded that most of the vertebral anomalies discussed arise during the embryonic period proper, although the timing of a few, such as spina bifida occulta, extends into the early fetal period. Images Fig. 1 Fig. 3 Fig. 5 PMID:3693103

  20. A one-dimensional model of PCP signaling: polarized cell behavior in the notochord of the ascidian Ciona

    PubMed Central

    Kourakis, Matthew J.; Reeves, Wendy; Newman-Smith, Erin; Maury, Benoit; Abdul-Wajid, Sarah; Smith, William C.

    2014-01-01

    Despite its importance in development and physiology the planar cell polarity (PCP) pathway remains one of the most enigmatic signaling mechanisms. The notochord of the ascidian Ciona provides a unique model for investigating the PCP pathway. Interestingly, the notochord appears to be the only embryonic structure in Ciona activating the PCP pathway. Moreover, the Ciona notochord as a single-file array of forty polarized cells is a uniquely tractable system for the study of polarization dynamics and the transmission of the PCP pathway. Here, we test models for propagation of a polarizing signal, interrogating temporal, spatial and signaling requirements. A simple cell-cell relay cascading through the entire length of the notochord is not supported; instead a more complex mechanism is revealed, with interactions influencing polarity between neighboring cells, but not distant ones. Mechanisms coordinating notochord-wide polarity remain elusive, but appear to entrain general (i.e., global) polarity even while local interactions remain important. However, this global polarizer does not appear to act as a localized, spatially-restricted determinant. Coordination of polarity along the long axis of the notochord requires the PCP pathway, a role we demonstrate is temporally distinct from this pathway’s earlier role in convergent extension and intercalation. We also reveal polarity in the notochord to be dynamic: a cell’s polarity state can be changed and then restored, underscoring the Ciona notochord’s amenability for in vivo studies of PCP. PMID:25173874

  1. The small molecule Mek1/2 inhibitor U0126 disrupts the chordamesoderm to notochord transition in zebrafish

    PubMed Central

    Hawkins, Thomas A; Cavodeassi, Florencia; Erdélyi, Ferenc; Szabó, Gábor; Lele, Zsolt

    2008-01-01

    Background Key molecules involved in notochord differentiation and function have been identified through genetic analysis in zebrafish and mice, but MEK1 and 2 have so far not been implicated in this process due to early lethality (Mek1-/-) and functional redundancy (Mek2-/-) in the knockout animals. Results Here, we reveal a potential role for Mek1/2 during notochord development by using the small molecule Mek1/2 inhibitor U0126 which blocks phosphorylation of the Mek1/2 target gene Erk1/2 in vivo. Applying the inhibitor from early gastrulation until the 18-somite stage produces a specific and consistent phenotype with lack of dark pigmentation, shorter tail and an abnormal, undulated notochord. Using morphological analysis, in situ hybridization, immunhistochemistry, TUNEL staining and electron microscopy, we demonstrate that in treated embryos the chordamesoderm to notochord transition is disrupted and identify disorganization in the medial layer of the perinotochordal basement mebrane as the probable cause of the undulations and bulges in the notochord. We also examined and excluded FGF as the upstream signal during this process. Conclusion Using the small chemical U0126, we have established a novel link between MAPK-signaling and notochord differentiation. Our phenotypic analysis suggests a potential connection between the MAPK-pathway, the COPI-mediated intracellular transport and/or the copper-dependent posttranslational regulatory processes during notochord differentiation. PMID:18419805

  2. Notochordal Cells in the Adult Intervertebral Disc: New Perspective on an Old Question

    PubMed Central

    Risbud, Makarand V.; Shapiro, Irving M.

    2011-01-01

    The intervertebral disc is a soft tissue, positioned between each of the vertebrae, that accommodates applied biomechanical forces to the spine. The central compartment of the disc contains the nucleus pulposus (NP), which is enclosed by the annulus fibrosus and the endplate cartilage. The NP is derived from the notochord, a rodlike structure of mesodermal origin. Development of the notochord is tightly regulated by interactive transcription factors and target genes. Since a number of these molecules are unique, they have been used for cell lineage and fate mapping studies of tissues of the intervertebral disc. These studies have shown that in a number of species including human, NP tissue retains notochordal cells throughout life. In the adult NP, there are present both large and small notochordal cells, as well as a progenitor cell population which can differentiate along the mesengenic pathway. Since tissue renewal in the intervertebral disc is dependent on the ability of these cells to commit to the NP lineage and undergo terminal differentiation, studies have been performed to assess which signaling pathways may regulate these activities. The notch signaling pathway is active in the intervertebral disc and is responsive to hypoxia, probably through HIF-1α. From a disease viewpoint, it is hypothesized that an oxemic shift, possibly mediated by alterations in the vascular supply to the tissues of the disc, would be expected to lead to a failure in notochordal progenitor cell activation and a decrease in the number of differentiated cells. In turn, this would lead to decrements in function and enhancement of the effect of agents that are known to promote disc degeneration. PMID:21967331

  3. Notochordal cells in the adult intervertebral disc: new perspective on an old question.

    PubMed

    Risbud, Makarand V; Shapiro, Irving M

    2011-01-01

    The intervertebral disc is a tissue positioned between each of the vertebrae that accommodates applied biomechanical forces to the spine. The central compartment of the disc contains the nucleus pulposus (NP) which is enclosed by the annulus fibrosus and the endplate cartilage.The NP is derived from the notochord, a rod-like structure of mesodermal origin. Development of the notochord is tightly regulated by interactive transcription factors and target genes. Since a number of these molecules are unique they have be used for cell lineage and fate mapping studies of tissues of the intervertebral disc. These studies have shown that in a number of species including human, NP tissue retains notochordal cells throughout life. In the adult NP, there are present both large and small notochordal cells, as well as a progenitor cell population which can differentiate along the mesengenic pathway. Since tissue renewal in the intervertebral disc is dependent on the ability of these cells to commit to the NP lineage and undergo terminal differentiation, studies have been performed to assess which signaling pathways may regulate these activities. The notch signaling pathway is active in the intervertebral disc and is responsive to hypoxia, probably through HIF-1a. From a disease viewpoint, it is hypothesized that an oxemic shift, possibly mediated by alterations in the vascular supply to the tissues of the disc would be expected to lead to a failure in notochordal progenitor cell activation and a decrease in the number of differentiated cells. In turn, this would lead to decrements in function and enhancement of the effect of agents that are known to promote disc degeneration.

  4. Sea Urchin Morphogenesis.

    PubMed

    McClay, David R

    2016-01-01

    In the sea urchin morphogenesis follows extensive molecular specification. The specification controls the many morphogenetic events and these, in turn, precede patterning steps that establish the larval body plan. To understand how the embryo is built it was necessary to understand those series of molecular steps. Here an example of the historical sequence of those discoveries is presented as it unfolded over the last 50 years, the years during which major progress in understanding development of many animals and plants was documented by CTDB. In sea urchin development a rich series of experimental studies first established many of the phenomenological components of skeletal morphogenesis and patterning without knowledge of the molecular components. The many discoveries of transcription factors, signals, and structural proteins that contribute to the shape of the endoskeleton of the sea urchin larva then followed as molecular tools became available. A number of transcription factors and signals were discovered that were necessary for specification, morphogenesis, and patterning. Perturbation of the transcription factors and signals provided the means for assembling models of the gene regulatory networks used for specification and controlled the subsequent morphogenetic events. The earlier experimental information informed perturbation experiments that asked how patterning worked. As a consequence it was learned that ectoderm provides a series of patterning signals to the skeletogenic cells and as a consequence the skeletogenic cells secrete a highly patterned skeleton based on their ability to genotypically decode the localized reception of several signals. We still do not understand the complexity of the signals received by the skeletogenic cells, nor do we understand in detail how the genotypic information shapes the secreted skeletal biomineral, but the current knowledge at least outlines the sequence of events and provides a useful template for future

  5. Sea Urchin Morphogenesis.

    PubMed

    McClay, David R

    2016-01-01

    In the sea urchin morphogenesis follows extensive molecular specification. The specification controls the many morphogenetic events and these, in turn, precede patterning steps that establish the larval body plan. To understand how the embryo is built it was necessary to understand those series of molecular steps. Here an example of the historical sequence of those discoveries is presented as it unfolded over the last 50 years, the years during which major progress in understanding development of many animals and plants was documented by CTDB. In sea urchin development a rich series of experimental studies first established many of the phenomenological components of skeletal morphogenesis and patterning without knowledge of the molecular components. The many discoveries of transcription factors, signals, and structural proteins that contribute to the shape of the endoskeleton of the sea urchin larva then followed as molecular tools became available. A number of transcription factors and signals were discovered that were necessary for specification, morphogenesis, and patterning. Perturbation of the transcription factors and signals provided the means for assembling models of the gene regulatory networks used for specification and controlled the subsequent morphogenetic events. The earlier experimental information informed perturbation experiments that asked how patterning worked. As a consequence it was learned that ectoderm provides a series of patterning signals to the skeletogenic cells and as a consequence the skeletogenic cells secrete a highly patterned skeleton based on their ability to genotypically decode the localized reception of several signals. We still do not understand the complexity of the signals received by the skeletogenic cells, nor do we understand in detail how the genotypic information shapes the secreted skeletal biomineral, but the current knowledge at least outlines the sequence of events and provides a useful template for future

  6. Morphogenesis by symbiogenesis

    NASA Technical Reports Server (NTRS)

    Chapman, M. J.; Margulis, L.

    1998-01-01

    Here we review cases where initiation of morphogenesis, including the differentiation of specialized cells and tissues, has clearly evolved due to cyclical symbiont integration. For reasons of space, our examples are drawn chiefly from the plant, fungal and bacterial kingdoms. Partners live in symbioses and show unique morphological specializations that result when they directly and cyclically interact. We include here brief citations to relevant literature where plant, bacterial or fungal partners alternate independent with entirely integrated living. The independent, or at least physically unassociated stages, are correlated with the appearance of distinctive morphologies that can be traced to the simultaneous presence and strong interaction of the plant with individuals that represent different taxa.

  7. Modeling plant morphogenesis.

    PubMed

    Prusinkiewicz, Przemyslaw; Rolland-Lagan, Anne-Gaëlle

    2006-02-01

    Applications of computational techniques to developmental plant biology include the processing of experimental data and the construction of simulation models. Substantial progress has been made in these areas over the past few years. Complex image-processing techniques are used to integrate sequences of two-dimensional images into three-dimensional descriptions of development over time and to extract useful quantitative traits. Large amounts of data are integrated into empirical models of developing plant organs and entire plants. Mechanistic models link molecular-level phenomena with the resulting phenotypes. Several models shed light on the possible properties of active auxin transport and its role in plant morphogenesis. PMID:16376602

  8. Modeling plant morphogenesis.

    PubMed

    Prusinkiewicz, Przemyslaw; Rolland-Lagan, Anne-Gaëlle

    2006-02-01

    Applications of computational techniques to developmental plant biology include the processing of experimental data and the construction of simulation models. Substantial progress has been made in these areas over the past few years. Complex image-processing techniques are used to integrate sequences of two-dimensional images into three-dimensional descriptions of development over time and to extract useful quantitative traits. Large amounts of data are integrated into empirical models of developing plant organs and entire plants. Mechanistic models link molecular-level phenomena with the resulting phenotypes. Several models shed light on the possible properties of active auxin transport and its role in plant morphogenesis.

  9. Human temporomandibular joint morphogenesis.

    PubMed

    Carini, Francesco; Scardina, Giuseppe Alessandro; Caradonna, Carola; Messina, Pietro; Valenza, Vincenzo

    2007-01-01

    Temporomandibular joint morphogenesis was studied. Ranging in age of fetuses examined was from 6 to14 weeks' gestation. Our results showed the condyle so first element that appear between 6 degrees and 8 degrees week (condylar blastema). After a week appear temporal elements. Disk appear at the same time of glenoid blastema and it reaches an advanced differentation before of the condyle and temporal element, so these don't effect machanical compression on mesenchyma where we find the disk. So we think that the disk result of genetic expression and it isn't the result of mechanical compression. The inferior joint cavity appear to 12 week. The superior joint cavity appear to 13-14 week. In conclusion, the appearance of the condyle is the first event during TMJ morphogenesis, with its initial bud, in form of a mesenchymal thickening, becoming detectable between the sixth and eight week of development, when all the large joints of the limbs are already well defined. PMID:18333411

  10. A zebrafish model of chordoma initiated by notochord-driven expression of HRASV12

    PubMed Central

    Burger, Alexa; Vasilyev, Aleksandr; Tomar, Ritu; Selig, Martin K.; Nielsen, G. Petur; Peterson, Randall T.; Drummond, Iain A.; Haber, Daniel A.

    2014-01-01

    Chordoma is a malignant tumor thought to arise from remnants of the embryonic notochord, with its origin in the bones of the axial skeleton. Surgical resection is the standard treatment, usually in combination with radiation therapy, but neither chemotherapeutic nor targeted therapeutic approaches have demonstrated success. No animal model and only few chordoma cell lines are available for preclinical drug testing, and, although no druggable genetic drivers have been identified, activation of EGFR and downstream AKT-PI3K pathways have been described. Here, we report a zebrafish model of chordoma, based on stable transgene-driven expression of HRASV12 in notochord cells during development. Extensive intra-notochordal tumor formation is evident within days of transgene expression, ultimately leading to larval death. The zebrafish tumors share characteristics of human chordoma as demonstrated by immunohistochemistry and electron microscopy. The mTORC1 inhibitor rapamycin, which has some demonstrated activity in a chordoma cell line, delays the onset of tumor formation in our zebrafish model, and improves survival of tumor-bearing fish. Consequently, the HRASV12-driven zebrafish model of chordoma could enable high-throughput screening of potential therapeutic agents for the treatment of this refractory cancer. PMID:24311731

  11. T gene isoform expression pattern is significantly different between chordomas and notochords.

    PubMed

    Wang, Ke; Hu, Qingtao; Wang, Liang; Chen, Wei; Tian, Kaibing; Cao, Chunwei; Wu, Zhen; Jia, Guijun; Zhang, Liwei; Zeng, Changqing; Zhang, Junting

    2015-11-13

    The T gene plays a key role in chordoma pathology. To investigate the role of T gene isoforms in chordoma, 22 skull base chordomas, three chordoma cell lines and 9 infant notochords, which were used as normal controls, were collected. We first conducted droplet digital PCR to quantify the absolute expression levels of the long and short isoforms of the T gene (T-long and T-short, respectively) and revealed that T-long was dominantly expressed in all chordomas and chordoma cell lines, but not in the notochords. The T-long/T-short ratio was significantly different between the chordomas and the notochords. Next, we validated the isoform expression pattern at protein expression level using Western blot in 9 chordomas. Furthermore, the T gene single nucleotide polymorphism site rs2305089, which is the only marker reported to be associated with chordomas, was sequenced in all of the chordoma samples. Association between rs2305089 and T-long/T-short ratio was not significant, indicating it was not involved in T gene alternative splicing. In conclusion, two T gene isoforms were investigated in skull base chordomas and chordoma cell lines, and the longer isoform was dominantly expressed. The distinct expression patterns of these T gene isoforms may contribute to the pathogenesis of skull base chordomas. However, further studies on the function of these isoforms are needed. PMID:26435504

  12. Emergent morphogenesis: elastic mechanics of a self-deforming tissue.

    PubMed

    Davidson, Lance A; Joshi, Sagar D; Kim, Hye Young; von Dassow, Michelangelo; Zhang, Lin; Zhou, Jian

    2010-01-01

    Multicellular organisms are generated by coordinated cell movements during morphogenesis. Convergent extension is a key tissue movement that organizes mesoderm, ectoderm, and endoderm in vertebrate embryos. The goals of researchers studying convergent extension, and morphogenesis in general, include understanding the molecular pathways that control cell identity, establish fields of cell types, and regulate cell behaviors. Cell identity, the size and boundaries of tissues, and the behaviors exhibited by those cells shape the developing embryo; however, there is a fundamental gap between understanding the molecular pathways that control processes within single cells and understanding how cells work together to assemble multicellular structures. Theoretical and experimental biomechanics of embryonic tissues are increasingly being used to bridge that gap. The efforts to map molecular pathways and the mechanical processes underlying morphogenesis are crucial to understanding: (1) the source of birth defects, (2) the formation of tumors and progression of cancer, and (3) basic principles of tissue engineering. In this paper, we first review the process of tissue convergent extension of the vertebrate axis and then review models used to study the self-organizing movements from a mechanical perspective. We conclude by presenting a relatively simple "wedge-model" that exhibits key emergent properties of convergent extension such as the coupling between tissue stiffness, cell intercalation forces, and tissue elongation forces. PMID:19815213

  13. Protocadherin-19 is essential for early steps in brain morphogenesis.

    PubMed

    Emond, Michelle R; Biswas, Sayantanee; Jontes, James D

    2009-10-01

    One of the earliest stages of brain morphogenesis is the establishment of the neural tube during neurulation. While some of the cellular mechanisms responsible for neurulation have been described in a number of vertebrate species, the underlying molecular processes are not fully understood. We have identified the zebrafish homolog of protocadherin-19, a member of the cadherin superfamily, which is expressed in the anterior neural plate and is required for brain morphogenesis. Interference with Protocadherin-19 function with antisense morpholino oligonucleotides leads to a severe disruption in early brain morphogenesis. Despite these pronounced effects on neurulation, axial patterning of the neural tube appears normal, as assessed by in situ hybridization for otx2, pax2.1 and krox20. Characterization of embryos early in development by in vivo 2-photon timelapse microscopy reveals that the observed disruption of morphogenesis results from an arrest of cell convergence in the anterior neural plate. These results provide the first functional data for protocadherin-19, demonstrating an essential role in early brain development.

  14. Cellular Morphogenesis In Silico

    PubMed Central

    Shinbrot, Troy; Chun, Young; Caicedo-Carvajal, Carlos; Foty, Ramsey

    2009-01-01

    Abstract We describe a model that simulates spherical cells of different types that can migrate and interact either attractively or repulsively. We find that both expected morphologies and previously unreported patterns spontaneously self-assemble. Among the newly discovered patterns are a segmented state of alternating discs, and a “shish-kebab” state, in which one cell type forms a ring around a second type. We show that these unique states result from cellular attraction that increases with distance (e.g., as membranes stretch viscoelastically), and would not be seen in traditional, e.g., molecular, potentials that diminish with distance. Most of the states found computationally have been observed in vitro, and it remains to be established what role these self-assembled states may play in in vivo morphogenesis. PMID:19686642

  15. Physics of Bacterial Morphogenesis

    PubMed Central

    Sun, Sean X.; Jiang, Hongyuan

    2011-01-01

    Summary: Bacterial cells utilize three-dimensional (3D) protein assemblies to perform important cellular functions such as growth, division, chemoreception, and motility. These assemblies are composed of mechanoproteins that can mechanically deform and exert force. Sometimes, small-nucleotide hydrolysis is coupled to mechanical deformations. In this review, we describe the general principle for an understanding of the coupling of mechanics with chemistry in mechanochemical systems. We apply this principle to understand bacterial cell shape and morphogenesis and how mechanical forces can influence peptidoglycan cell wall growth. We review a model that can potentially reconcile the growth dynamics of the cell wall with the role of cytoskeletal proteins such as MreB and crescentin. We also review the application of mechanochemical principles to understand the assembly and constriction of the FtsZ ring. A number of potential mechanisms are proposed, and important questions are discussed. PMID:22126993

  16. Geometric control of tissue morphogenesis

    PubMed Central

    Nelson, Celeste M.

    2009-01-01

    Summary Morphogenesis is the dynamic and regulated change in tissue form that leads to creation of the body plan and development of mature organs. Research over the past several decades has uncovered a multitude of genetic factors required for morphogenesis in animals. The behaviors of individual cells within a developing tissue are determined by combining these genetic signals with information from the surrounding microenvironment. At any point in time, the local microenvironment is influenced by macroscale tissue geometry, which sculpts long range signals by affecting gradients of morphogens and mechanical stresses. The geometry of a tissue thus acts as both a template and instructive cue for further morphogenesis. PMID:19167433

  17. Molecular control of endothelial cell behaviour during blood vessel morphogenesis

    PubMed Central

    Herbert, Shane P.; Stainier, Didier Y.R.

    2012-01-01

    The vertebrate vasculature forms an extensive branched network of blood vessels that supplies tissues with nutrients and oxygen. During vascular development, coordinated control of endothelial cell behaviour at the levels of cell migration, proliferation, polarity, differentiation and cell–cell communication is critical for functional blood vessel morphogenesis. Recent data uncover elaborate transcriptional, post-transcriptional and post-translational mechanisms that fine-tune key signalling pathways (such as the vascular endothelial growth factor and Notch pathways) to control endothelial cell behaviour during blood vessel sprouting (angiogenesis). These emerging frameworks controlling angiogenesis provide unique insights into fundamental biological processes common to other systems, such as tissue branching morphogenesis, mechanotransduction and tubulogenesis. PMID:21860391

  18. Morphogenesis of Bittner Virus

    PubMed Central

    Gay, Frederick W.; Clarke, John K.; Dermott, Evelyn

    1970-01-01

    The morphogenesis of Bittner virus (mouse mammary tumor virus) was studied in sectioned mammary tumor cells. Internal components of the virus (type A particles) were seen being assembled in virus factories close to the nucleus and were also seen forming at the plasma membrane. The particles in virus factories became enveloped by budding through the membrane of cytoplasmic vacuoles which were derived from dilated endoplasmic reticulum. Complete virus particles were liberated from these vacuoles by cell lysis. Particles budding at the plasma membrane were released into intercellular spaces. Maturation of enveloped virus occurred after release, but mature internal components were rarely seen in the cytoplasm before envelopment. Direct cell-to-cell transfer of virus by pinocytosis of budding particles by an adjacent cell was observed, and unusual forms of budding virus which participated in this process are illustrated and described. There was evidence that some virus particles contained cytoplasmic constituents, including ribosomes. Certain features of the structure of internal components are discussed in relation to a recently proposed model for the internal component of the mouse leukemia virus. Intracisternal virus-like particles were occasionally seen in tumor cells, but there was no evidence that these structures were developmentally related to Bittner virus. Images PMID:4193837

  19. Morphogenesis of Bittner virus.

    PubMed

    Gay, F W; Clarke, J K; Dermott, E

    1970-06-01

    The morphogenesis of Bittner virus (mouse mammary tumor virus) was studied in sectioned mammary tumor cells. Internal components of the virus (type A particles) were seen being assembled in virus factories close to the nucleus and were also seen forming at the plasma membrane. The particles in virus factories became enveloped by budding through the membrane of cytoplasmic vacuoles which were derived from dilated endoplasmic reticulum. Complete virus particles were liberated from these vacuoles by cell lysis. Particles budding at the plasma membrane were released into intercellular spaces. Maturation of enveloped virus occurred after release, but mature internal components were rarely seen in the cytoplasm before envelopment. Direct cell-to-cell transfer of virus by pinocytosis of budding particles by an adjacent cell was observed, and unusual forms of budding virus which participated in this process are illustrated and described. There was evidence that some virus particles contained cytoplasmic constituents, including ribosomes. Certain features of the structure of internal components are discussed in relation to a recently proposed model for the internal component of the mouse leukemia virus. Intracisternal virus-like particles were occasionally seen in tumor cells, but there was no evidence that these structures were developmentally related to Bittner virus. PMID:4193837

  20. Difficulty distinguishing benign notochordal cell tumor from chordoma further suggests a link between them

    PubMed Central

    2014-01-01

    Background Much discussion about benign notochordal cell tissue in vertebrae has centered on the nature of its relationship, if any, to chordoma. Often referred to as benign notochordal cell tumors (BNCTs), these lesions have unique morphological features, however, differentiating between notochordal cells in discs, BNCT, and chordoma can be difficult. They are described as radiologically distinct from chordoma, with lysis, contrast enhancement, and a soft tissue mass indicating chordoma. Methods All chordomas diagnosed at our institution, the Istituto Ortopedico Rizzoli (Bologna, Italy), prior to 2008 were reviewed, yielding 174 cases. Five were limited to bone; one was a recurrent chordoma without original data available. The remaining four were re-evaluated in detail. Results There were three women and one man, aged 33–57 years (mean, 48 years). Two were BNCTs and two were mixed lesions containing BNCT and chordoma. On computed tomography, all were radiopaque with areas of lysis. One BNCT was heterogeneous on magnetic resonance imaging, enhancing after contrast. Microscopically, one BNCT had a well-defined cystic area with a sclerotic border. The other had a minute atypical area; it recurred as chordoma. The mixed lesions had areas of definitive BNCT, definitive chordoma, and atypical areas that did not meet the criteria for either. The atypical areas in all three cases ‘blended’ with areas of chordoma or BNCT. Conclusion These cases illustrate the ongoing challenges in differentiating between BNCT and chordoma. All had unique imaging features; three had atypical microscopic areas blending with BNCT or chordoma, strengthening the argument for a relationship between the two entities and supporting the idea that some BNCTs may progress to chordoma. Our study dispels the notion that any single radiologic criterion used to distinguish between chordoma and BNCT is reliable, opening the discussion as to whether or how to monitor BNCTs. PMID:25609192

  1. Generation of knock-in mice that express nuclear enhanced green fluorescent protein and tamoxifen-inducible Cre recombinase in the notochord from Foxa2 and T loci.

    PubMed

    Imuta, Yu; Kiyonari, Hiroshi; Jang, Chuan-Wei; Behringer, Richard R; Sasaki, Hiroshi

    2013-03-01

    The node and the notochord are important embryonic signaling centers that control embryonic pattern formation. Notochord progenitor cells present in the node and later in the posterior end of the notochord move anteriorly to generate the notochord. To understand the dynamics of cell movement during notochord development and the molecular mechanisms controlling this event, analyses of cell movements using time-lapse imaging and conditional manipulation of gene activities are required. To achieve this goal, we generated two knock-in mouse lines that simultaneously express nuclear enhanced green fluorescent protein (EGFP) and tamoxifen-inducible Cre, CreER(T2) , from two notochord gene loci, Foxa2 and T (Brachury). In Foxa2(nEGFP-CreERT2/+) and T(nEGFP-CreERT2/+) embryos, nuclei of the Foxa2 or T-expressing cells, which include the node, notochord, and endoderm (Foxa2) or wide range of posterior mesoderm (T), were labeled with EGFP at intensities that can be used for live imaging. Cre activity was also induced in cells expressing Foxa2 and T 1 day after tamoxifen administration. These mice are expected to be useful tools for analyzing the mechanisms of notochord development.

  2. Morphogenesis: a Mob rules from the rear.

    PubMed

    Chalker, Douglas L; Frankel, Joseph

    2014-08-01

    The giant ciliated protozoan Stentor coeruleus is re-emerging as a model organism for morphogenesis and patterning in unicellular organisms. A new study provides evidence that cytokinesis and morphogenesis are mechanistically linked through the Mob1 protein. PMID:25093564

  3. The control of branching morphogenesis

    PubMed Central

    Iber, Dagmar; Menshykau, Denis

    2013-01-01

    Many organs of higher organisms are heavily branched structures and arise by an apparently similar process of branching morphogenesis. Yet the regulatory components and local interactions that have been identified differ greatly in these organs. It is an open question whether the regulatory processes work according to a common principle and how far physical and geometrical constraints determine the branching process. Here, we review the known regulatory factors and physical constraints in lung, kidney, pancreas, prostate, mammary gland and salivary gland branching morphogenesis, and describe the models that have been formulated to analyse their impacts. PMID:24004663

  4. Ontogeny of the vertebral column of Eleutherodactylus johnstonei (Anura: Eleutherodactylidae) reveals heterochronies relative to metamorphic frogs.

    PubMed

    Meza-Joya, Fabio Leonardo; Ramos-Pallares, Eliana Patricia; Ramírez-Pinilla, Martha Patricia

    2013-07-01

    Over the last century, the morphogenesis of the vertebral column has been considered as a highly conserved process among anurans. This statement is based on the study of few metamorphic taxa, ignoring the role of developmental mechanisms underlying the evolution of specialized life-histories. Direct development in anurans has been regarded as evolutionarily derived and involves developmental recapitulation and repatterning at different levels in all amphibian taxa studied so far. Herein, we analyze the vertebral column morphogenesis of the direct-developing frog Eleutherodactylus johnstonei, describing the sequence of chondrification and ossification, based on cleared and double-stained specimens from early stage embryos to adults. In general, our results show that the morphogenesis of the vertebral column in E. johnstonei recapitulates the ancestral tadpole-like pattern of development. However, the analysis of the sequence of events using heterochrony plots shows important heterocronies relative to metamorphic species, such as a delay in the chondrification of the vertebral centra and in osteogenesis. These ontogenetic peculiarities may represent derived traits in direct-developing frogs and are possibly correlated with its unusual life history. In addition, several features of the vertebral column of E. johnstonei are highly variable from its typical morphology. We report some malformations and small deviations, which do not seem to affect the survival of individuals. These anomalies have also been found in other frogs, and include many vertebral defects, such as vertebral fusion, and vertebral preclusion and/or induction.

  5. Chemotactic collapse and mesenchymal morphogenesis

    NASA Astrophysics Data System (ADS)

    Escudero, Carlos

    2005-08-01

    We study the effect of chemotactic signaling among mesenchymal cells. We show that the particular physiology of the mesenchymal cells allows one-dimensional collapse in contrast to the case of bacteria, and that the mesenchymal morphogenesis represents thus a more complex type of pattern formation than those found in bacterial colonies. We compare our theoretical predictions with recent in vitro experiments.

  6. Regulation of neurocoel morphogenesis by Pard6 gamma b.

    PubMed

    Munson, Chantilly; Huisken, Jan; Bit-Avragim, Nana; Kuo, Taiyi; Dong, P D; Ober, Elke A; Verkade, Heather; Abdelilah-Seyfried, Salim; Stainier, Didier Y R

    2008-12-01

    The Par3/Par6/aPKC protein complex plays a key role in the establishment and maintenance of apicobasal polarity, a cellular characteristic essential for tissue and organ morphogenesis, differentiation and homeostasis. During a forward genetic screen for liver and pancreas mutants, we identified a pard6gammab mutant, representing the first known pard6 mutant in a vertebrate organism. pard6gammab mutants exhibit defects in epithelial tissue development as well as multiple lumens in the neural tube. Analyses of the cells lining the neural tube cavity, or neurocoel, in wildtype and pard6gammab mutant embryos show that lack of Pard6gammab function leads to defects in mitotic spindle orientation during neurulation. We also found that the PB1 (aPKC-binding) and CRIB (Cdc-42-binding) domains and the KPLG amino acid sequence within the PDZ domain (Pals1-and Crumbs binding) are not required for Pard6gammab localization but are essential for its function in neurocoel morphogenesis. Apical membranes are reduced, but not completely absent, in mutants lacking the zygotic, or both the maternal and zygotic, function of pard6gammab, leading us to examine the localization and function of the three additional zebrafish Pard6 proteins. We found that Pard6alpha, but not Pard6beta or Pard6gammaa, could partially rescue the pard6gammab(s441) mutant phenotypes. Altogether, these data indicate a previously unappreciated functional diversity and complexity within the vertebrate pard6 gene family.

  7. The effect of novel nitrogen-rich plasma polymer coatings on the phenotypic profile of notochordal cells

    PubMed Central

    Mwale, Fackson; Wang, Hong Tian; Petit, Alain; Girard-Lauriault, Pierre-Luc; Hunter, Christopher J; Ouellet, Jean A; Wertheimer, Michael R; Antoniou, John

    2007-01-01

    Background The loss of the notochordal cells from the nucleus pulposus is associated with ageing and disc degeneration. However, understanding the mechanisms responsible for the loss of these cells has been hampered in part due to the difficulty of culturing and maintaining their phenotype. Furthermore, little is known about the influence of the substratum on the molecular markers of notochordal cells. Methods Notochordal cells were isolated from lumbar spine of non-chondrodystrophoid dogs and cultured on N-rich plasma polymer layers, so-called "PPE:N" (N-doped plasma-polymerised ethylene, containing up to 36% [N]) surfaces, for 3, 7 or 14 days. Gene expression of vimentin (VIM), pleiotrophin (PTN), matrix Gla protein (MGP), cartilage oligomeric matrix protein (COMP), keratin 18 (KRT 18), aggrecan (AGG), collagen type 1 (COL1A2), collagen type 2 (COL2A1) was analyzed through semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results Notochordal cells were maintained in culture on PPE:N for up to 14 days with no loss in cell viability. Except for VIM, gene expression varied depending on the culture periods and [N] concentration of the substratum. Generally, PPE:N surfaces altered gene expression significantly when cells were cultured for 3 or 7 days. Conclusion The present study has shown that notochordal cells from dogs can attach to and grow on PPE:N surfaces. Analysis of the expression of different genes in these cells cultured on different N-functionalized surfaces indicates that cellular behaviour is gene-specific and time-dependent. Further studies are required to better understand the roles of specific surface functionalities on receptor sites, and their effects on cellular phenotypes. PMID:17822560

  8. Proposed Diagnostic Criteria, Classification Schema, and Review of Literature of Notochord-Derived Ecchordosis Physaliphora

    PubMed Central

    Lagman, Carlito; Sarmiento, J. Manuel; Turtz, Alan R; Chitale, Rohan V

    2016-01-01

    Ecchordosis physaliphora (EP) is a benign notochordal remnant derived from ectopic nests found along the craniospinal axis. It typically presents asymptomatically and is diagnosed using classic radiologic features, particularly location, T1-hypointensity, T2-hyperintensity, and lack of enhancement following gadolinium (Gd) contrast administration. Distinguishing EP from its malignant counterpart, chordoma, is of paramount importance, given the aggressive nature of the latter. Advances in imaging and immunohistochemistry have aided in diagnosis to an extent but, to our knowledge, identification of the genetic fingerprint of EP has yet to take place. Further cytological analysis of these lesions in search of a genetic link is warranted. We propose here a set of diagnostic criteria based on features consistently cited in the literature. In this literature review, 23 case reports were identified and collated into a summary of symptomatic cases of ecchordosis physaliphora. An illustrative case report of two patients was also included.  PMID:27158576

  9. Heart fields and cardiac morphogenesis.

    PubMed

    Kelly, Robert G; Buckingham, Margaret E; Moorman, Antoon F

    2014-10-01

    In this review, we focus on two important steps in the formation of the embryonic heart: (i) the progressive addition of late differentiating progenitor cells from the second heart field that drives heart tube extension during looping morphogenesis, and (ii) the emergence of patterned proliferation within the embryonic myocardium that generates distinct cardiac chambers. During the transition between these steps, the major site of proliferation switches from progenitor cells outside the early heart to proliferation within the embryonic myocardium. The second heart field and ballooning morphogenesis concepts have major repercussions on our understanding of human heart development and disease. In particular, they provide a framework to dissect the origin of congenital heart defects and the regulation of myocardial proliferation and differentiation of relevance for cardiac repair.

  10. Developmental expression of Hsp90, Hsp70 and HSF during morphogenesis in the vetigastropod Haliotis asinina.

    PubMed

    Gunter, Helen M; Degnan, Bernard M

    2007-08-01

    Heat shock proteins (Hsps) have dual functions, participating in both the stress response and a broad range of developmental processes. At physiological temperatures, it has been demonstrated in deuterostomes (vertebrates) and ecdysozoans (insects) that Hsps are expressed in tissues that are undergoing differentiation and morphogenesis. Here we investigate the developmental expression of Hsp70, Hsp90 and their regulatory transcription factor heat shock transcription factor (HSF) in the marine gastropod Haliotis asinina, a representative of the 3rd major lineage of bilaterian animals, the Lophotrochozoa. HasHsp70, HasHsp90 and HasHSF are maternally expressed in H. asinina and are progressively restricted to the micromere lineage during cleavage. During larval morphogenesis, they are expressed in unique and overlapping patterns in the prototroch, foot, and mantle. Hsp expression peaked in these tissues during periods of cell differentiation and morphogenesis, returning to lower levels after morphogenesis was complete. These patterns of Hsp and HSF expression in H. asinina are akin to those observed in ecdysozoans and deuterostomes, with Hsps being activated in cells and tissues undergoing morphogenesis.

  11. Osmoregulatory function of large vacuoles found in notochordal cells of the intervertebral disc running title: an osmoregulatory vacuole.

    PubMed

    Hunter, Christopher J; Bianchi, Sophia; Cheng, Phil; Muldrew, Ken

    2007-12-01

    The nucleus pulposi of many species contain residual cells from the embryonic notochord, which exhibit a very unusual appearance (large vacuoles occupying approximately 80% of the cell volume, surrounded by an actin cytoskeleton). While the vacuoles have been qualitatively described, their composition and function has remained elusive. Given that these cells are believed to generate and experience significant osmotic pressures in both the notochord and intervertebral disc, we hypothesized that the vacuoles may serve as osmoregulatory organelles. Using both experimental and theoretical means, we demonstrated that the vacuoles contain a low-osmolality solution, generated via ion pumps on the vacuolar membrane. During hypotonic stress the vacuoles release their contents into the cytoplasm, diluting the cytoplasm and restoring the osmotic balance across the cell membrane. Thus the vacuoles function to regulate the cell volume and tonicity during rapid osmotic stress, protecting the cells from potentially damaging swelling pressures.

  12. Transcriptome analysis of vertebral bone in the flounder, Paralichthys olivaceus (Teleostei, Pleuronectiformes), using Illumina sequencing.

    PubMed

    Ibaraki, Harumi; Wu, Xiaoming; Uji, Susumu; Yokoi, Hayato; Sakai, Yoshifumi; Suzuki, Tohru

    2015-12-01

    The processes underlying vertebral development in teleosts and tetrapods differ markedly in a variety of ways. At present, the molecular basis of teleost vertebral development and growth is poorly understood. Understanding vertebral development at the molecular level is important for aquaculture to prevent vertebral anomalies that can arise from a variety of factors, including excess vitamin A (all-trans retinol, VA) in the diet. To facilitate studies on teloest vertebral development, we performed transcriptome analysis of four month old flounder, Paralichthys olivaceus, vertebrae using next-generation sequencing. Expression profile obtained demonstrates that some members of the hh, bmp, fgf, wnt gene families, and their receptors, hox, pax, sox, dlx and tbx gene families and ntl, which are known to function in notochord and somite development in embryos, are expressed in the vertebrae. It was also showed that in addition to the retinoic acid receptor (Rar), the vertebrae express alcohol dehydrogenase 1 and retinal dehydrogenase 2 which convert VA to all-trans-retinoic acid (RA). The assembled contigs also included cytochrome p450 family members, which inactivate RA, as well as phosphatidylcholine-retinol O-acetyltransferase, which converts VA to all-trans-retinyl ester, a stock form of VA. These data suggest that in teleost vertebrae, expression of various signals and transcription factors which function in the notochord and somite development is maintained until adult stage, and RA metabolism and signaling are active to regulate transcription of RA-responsible genes, such as hedgehog and hox genes. This is the first transcriptome analysis of teleost fish vertebrae. PMID:26452303

  13. Silencing the Morphogenesis of Rotavirus

    PubMed Central

    López, Tomas; Camacho, Minerva; Zayas, Margarita; Nájera, Rebeca; Sánchez, Rosana; Arias, Carlos F.; López, Susana

    2005-01-01

    The morphogenesis of rotaviruses follows a unique pathway in which immature double-layered particles (DLPs) assembled in the cytoplasm bud across the membrane of the endoplasmic reticulum (ER), acquiring during this process a transient lipid membrane which is modified with the ER resident viral glycoproteins NSP4 and VP7; these enveloped particles also contain VP4. As the particles move towards the interior of the ER cisternae, the transient lipid membrane and the nonstructural protein NSP4 are lost, while the virus surface proteins VP4 and VP7 rearrange to form the outermost virus protein layer, yielding mature infectious triple-layered particles (TLPs). In this work, we have characterized the role of NSP4 and VP7 in rotavirus morphogenesis by silencing the expression of both glycoproteins through RNA interference. Silencing the expression of either NSP4 or VP7 reduced the yield of viral progeny by 75 to 80%, although the underlying mechanism of this reduction was different in each case. Blocking the synthesis of NSP4 affected the intracellular accumulation and the cellular distribution of several viral proteins, and little or no virus particles (neither DLPs nor TLPs) were assembled. VP7 silencing, in contrast, did not affect the expression or distribution of other viral proteins, but in its absence, enveloped particles accumulated within the lumen of the ER, and no mature infectious virus was produced. Altogether, these results indicate that during a viral infection, NSP4 serves as a receptor for DLPs on the ER membrane and drives the budding of these particles into the ER lumen, while VP7 is required for removing the lipid envelope during the final step of virus morphogenesis. PMID:15596814

  14. Eye Morphogenesis and Patterning of the Optic Vesicle

    PubMed Central

    Fuhrmann, Sabine

    2010-01-01

    Organogenesis of the eye is a multi-step process that starts with the formation of optic vesicles followed by invagination of the distal domain of the vesicles and the overlying lens placode resulting in morphogenesis of the optic cup. The late optic vesicle becomes patterned into distinct ocular tissues; the neural retina, retinal pigment epithelium (RPE) and optic stalk. Multiple congenital eye disorders, including anophthalmia or microphthalmia, aniridia, coloboma and retinal dysplasia, stem from disruptions in embryonic eye development. Thus, it is critical to understand the mechanisms that lead to initial specification and differentiation of ocular tissues. An accumulating number of studies demonstrate that a complex interplay between inductive signals provided by tissue-tissue interactions and cell-intrinsic factors is critical to ensure proper specification of ocular tissues as well as maintenance of RPE cell fate. While several of the extrinsic and intrinsic determinants have been identified, we are just at the beginning to understand how these signals are integrated. In addition, we know very little about the actual output of these interactions. In this chapter, we provide an update of the mechanisms controlling early steps of eye development in vertebrates, with emphasis on optic vesicle evagination, specification of neural retina and RPE at the optic vesicle stage, the process of invagination during morphogenesis of the optic cup and maintenance of the RPE cell fate. PMID:20959163

  15. Regulation of neurocoel morphogenesis by Pard6γb

    PubMed Central

    Munson, Chantilly; Huisken, Jan; Bit-Avragim, Nana; Kuo, Taiyi; Dong, P.D.; Ober, Elke A.; Verkade, Heather; Abdelilah-Seyfried, Salim; Stainier, Didier Y.R

    2008-01-01

    Summary The Par3/Par6/aPKC protein complex plays a key role in the establishment and maintenance of apicobasal polarity, a cellular characteristic essential for tissue and organ morphogenesis, differentiation and homeostasis. During a forward genetic screen for liver and pancreas mutants, we identified a pard6γb mutant, representing the first known pard6 mutant in a vertebrate organism. pard6γb mutants exhibit defects in epithelial tissue development as well as multiple lumens in the neural tube. Analyses of the cells lining the neural tube cavity, or neurocoel, in wildtype and pard6γb mutant embryos show that lack of Pard6γb function leads to defects in mitotic spindle orientation during neurulation. We also found that the PB1 (aPKC-binding) and CRIB (Cdc-42-binding) domains and the KPLG amino acid sequence within the PDZ domain (Pals1- and Crumbs binding) are not required for Pard6γb localization but are essential for its function in neurocoel morphogenesis. Apical membranes are reduced, but not completely absent, in mutants lacking the zygotic, or both the maternal and zygotic, function of pard6γb, leading us to examine the localization and function of the three additional zebrafish Pard6 proteins. We found that Pard6α, but not Pard6β or Pard6γa, could partially rescue the pard6γbs441 mutant phenotypes. Altogether, these data indicate a previously unappreciated functional diversity and complexity within the vertebrate pard6 gene family. PMID:18817769

  16. Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish.

    PubMed

    Lovely, C Ben; Swartz, Mary E; McCarthy, Neil; Norrie, Jacqueline L; Eberhart, Johann K

    2016-06-01

    The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. PMID:27122171

  17. An overview of cardiac morphogenesis.

    PubMed

    Schleich, Jean-Marc; Abdulla, Tariq; Summers, Ron; Houyel, Lucile

    2013-11-01

    Accurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8 weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In this article we review the different steps of heart development, focusing on the processes of alignment and septation. We also show, as often as possible, the links between abnormalities of cardiac development and the main congenital heart defects. The development of animal models has permitted the unraveling of many mechanisms that potentially lead to cardiac malformations. A next step towards a better knowledge of cardiac development could be multiscale cardiac modelling. PMID:24138816

  18. Cellular and physical mechanisms of branching morphogenesis

    PubMed Central

    Varner, Victor D.; Nelson, Celeste M.

    2014-01-01

    Branching morphogenesis is the developmental program that builds the ramified epithelial trees of various organs, including the airways of the lung, the collecting ducts of the kidney, and the ducts of the mammary and salivary glands. Even though the final geometries of epithelial trees are distinct, the molecular signaling pathways that control branching morphogenesis appear to be conserved across organs and species. However, despite this molecular homology, recent advances in cell lineage analysis and real-time imaging have uncovered surprising differences in the mechanisms that build these diverse tissues. Here, we review these studies and discuss the cellular and physical mechanisms that can contribute to branching morphogenesis. PMID:25005470

  19. Concordia discors: duality in the origin of the vertebrate tail.

    PubMed

    Handrigan, Gregory R

    2003-03-01

    The vertebrate tail is an extension of the main body axis caudal to the anus. The developmental origin of this structure has been a source of debate amongst embryologists for the past century. Some view tail development as a continuation of the morphogenetic processes that shape the head and trunk (i.e. gastrulation). The alternative view, secondary development, holds that the tail forms in a manner similar to limb development, i.e. by secondary induction. Previous developmental studies have provided support for both views. Here I revisit these studies, describing caudal morphogenesis in select vertebrates, the associated genes and developmental defects, and, as a relevant aside, consider the developmental and evolutionary relationships of primary and secondary neurulation. I conclude that caudal development enlists both gastrulation and secondary induction, and that the application of recent high-resolution cell labelling technology may clarify how these discordant programmes interact in building the vertebrate tail.

  20. The identification of transcription factors expressed in the notochord of Ciona intestinalis adds new potential players to the Brachyury gene regulatory network

    PubMed Central

    José-Edwards, Diana S.; Kerner, Pierre; Kugler, Jamie E.; Deng, Wei; Jiang, Di; Di Gregorio, Anna

    2013-01-01

    The notochord is the distinctive characteristic of chordates; however, the knowledge of the complement of transcription factors governing the development of this structure is still incomplete. Here we present the expression patterns of seven transcription factor genes detected in the notochord of the ascidian Ciona intestinalis at various stages of embryonic development. Four of these transcription factors, Fos-a, NFAT5, AFF and Klf15, have not been directly associated with the notochord in previous studies, while the others, including Spalt-like-a, Lmx-like and STAT5/6-b, display evolutionarily conserved expression in this structure as well as in other domains. We examined the hierarchical relationships between these genes and the transcription factor Brachyury, which is necessary for notochord development in all chordates. We found that Ciona Brachyury regulates the expression of most, although not all, of these genes. These results shed light on the genetic regulatory program underlying notochord formation in Ciona and possibly other chordates. PMID:21594950

  1. Coordinating cell and tissue behavior during zebrafish neural tube morphogenesis.

    PubMed

    Araya, Claudio; Ward, Laura C; Girdler, Gemma C; Miranda, Miguel

    2016-03-01

    The development of a vertebrate neural epithelium with well-organized apico-basal polarity and a central lumen is essential for its proper function. However, how this polarity is established during embryonic development and the potential influence of surrounding signals and tissues on such organization has remained less understood. In recent years the combined superior transparency and genetics of the zebrafish embryo has allowed for in vivo visualization and quantification of the cellular and molecular dynamics that govern neural tube structure. Here, we discuss recent studies revealing how co-ordinated cell-cell interactions coupled with adjacent tissue dynamics are critical to regulate final neural tissue architecture. Furthermore, new findings show how the spatial regulation and timing of orientated cell division is key in defining precise lumen formation at the tissue midline. In addition, we compare zebrafish neurulation with that of amniotes and amphibians in an attempt to understand the conserved cellular mechanisms driving neurulation and resolve the apparent differences among animals. Zebrafish neurulation not only offers fundamental insights into early vertebrate brain development but also the opportunity to explore in vivo cell and tissue dynamics during complex three-dimensional animal morphogenesis.

  2. Cell-intrinsic drivers of dendrite morphogenesis

    PubMed Central

    Puram, Sidharth V.; Bonni, Azad

    2013-01-01

    The proper formation and morphogenesis of dendrites is fundamental to the establishment of neural circuits in the brain. Following cell cycle exit and migration, neurons undergo organized stages of dendrite morphogenesis, which include dendritic arbor growth and elaboration followed by retraction and pruning. Although these developmental stages were characterized over a century ago, molecular regulators of dendrite morphogenesis have only recently been defined. In particular, studies in Drosophila and mammalian neurons have identified numerous cell-intrinsic drivers of dendrite morphogenesis that include transcriptional regulators, cytoskeletal and motor proteins, secretory and endocytic pathways, cell cycle-regulated ubiquitin ligases, and components of other signaling cascades. Here, we review cell-intrinsic drivers of dendrite patterning and discuss how the characterization of such crucial regulators advances our understanding of normal brain development and pathogenesis of diverse cognitive disorders. PMID:24255095

  3. Shrinking the hammer: micromechanical approaches to morphogenesis.

    PubMed

    Milani, Pascale; Braybrook, Siobhan A; Boudaoud, Arezki

    2013-11-01

    Morphogenesis, the remarkable process by which a developing organism achieves its shape, relies on the coordinated growth of cells, tissues, and organs. While the molecular and genetic basis of morphogenesis is starting to be unravelled, understanding shape changes is lagging behind. Actually, shape is imposed by the structural elements of the organism, and the translation of cellular activity into morphogenesis must go through these elements. Therefore, many methods have been developed recently to quantify, at cellular resolution, the properties of the main structural element in plants, the cell wall. As plant cell growth is restrained by the cell wall and powered by turgor pressure, such methods also address the quantification of turgor. These different micromechanical approaches are reviewed here, with a critical assessment of their strengths and weaknesses, and a discussion of how they can help us understand the regulation of growth and morphogenesis.

  4. Notochordal cells protect nucleus pulposus cells from degradation and apoptosis: implications for the mechanisms of intervertebral disc degeneration

    PubMed Central

    2011-01-01

    Introduction The relative resistance of non-chondrodystrophic (NCD) canines to degenerative disc disease (DDD) may be due to a combination of anabolic and anti-catabolic factors secreted by notochordal cells within the intervertebral disc (IVD) nucleus pulposus (NP). Factors known to induce DDD include interleukin-1 beta (IL-1ß) and/or Fas-Ligand (Fas-L). Therefore we evaluated the ability of notochordal cell conditioned medium (NCCM) to protect NP cells from IL-1ß and IL-1ß +FasL-mediated cell death and degeneration. Methods We cultured bovine NP cells with IL-1ß or IL-1ß+FasL under hypoxic serum-free conditions (3.5% O2) and treated the cells with either serum-free NCCM or basal medium (Advanced DMEM/F-12). We used flow cytometry to evaluate cell death and real-time (RT-)PCR to determine the gene expression of aggrecan, collagen 2, and link protein, mediators of matrix degradation ADAMTS-4 and MMP3, the matrix protection molecule TIMP1, the cluster of differentiation (CD)44 receptor, the inflammatory cytokine IL-6 and Ank. We then determined the expression of specific apoptotic pathways in bovine NP cells by characterizing the expression of activated caspases-3, -8 and -9 in the presence of IL-1ß+FasL when cultured with NCCM, conditioned medium obtained using bovine NP cells (BCCM), and basal medium all supplemented with 2% FBS. Results NCCM inhibits bovine NP cell death and apoptosis via suppression of activated caspase-9 and caspase-3/7. Furthermore, NCCM protects NP cells from the degradative effects of IL-1ß and IL-1ß+Fas-L by up-regulating the expression of anabolic/matrix protective genes (aggrecan, collagen type 2, CD44, link protein and TIMP-1) and down-regulating matrix degrading genes such as MMP-3. Expression of ADAMTS-4, which encodes a protein for aggrecan remodeling, is increased. NCCM also protects against IL-1+FasL-mediated down-regulation of Ank expression. Furthermore, NP cells treated with NCCM in the presence of IL-1ß+Fas-L down

  5. Zebrafish eleutheroembryos as an alternative system for screening chemicals disrupting the mammalian thyroid gland morphogenesis and function.

    PubMed

    Raldúa, Demetrio; Thienpont, Benedicte; Babin, Patrick J

    2012-04-01

    The importance and irreversibility of the effects of thyroid hormone deficiency on human brain development highlight the importance of identifying environmental agents that interfere with thyroid gland morphogenesis and function. Zebrafish eleutheroembryos are currently used by many pharmaceutical companies in drug discovery as a vertebrate model, not subjected to regulations for animal experiments, that provides an intermediate step between in vitro and rodent assay. The mechanisms of zebrafish thyroid development are generally comparable to those in humans, and moreover, molecular and functional studies of zebrafish thyroid follicles have demonstrated a high degree of conservation with upper vertebrates, opening up the possibility of designing alternative methods for screening individual chemicals and mixtures that impairing thyroid gland morphogenesis and/or function. Analysis of the intrafollicular thyroxine-content of zebrafish larvae exposed to potential disruptors has proved to be a reliable, physiologically relevant endpoint to estimate effects of chemicals on the mammalian thyroid gland. PMID:21978863

  6. Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord‐specific markers during early human intervertebral disc development

    PubMed Central

    Rodrigues‐Pinto, Ricardo; Berry, Andrew; Piper‐Hanley, Karen; Hanley, Neil; Richardson, Stephen M.

    2016-01-01

    ABSTRACT In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte‐like cells. Although animal studies indicate that notochord‐derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5–18 weeks post‐conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E‐cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co‐expressed by sclerotomal cells. CD90, Tie2, and E‐cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord‐specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327–1340, 2016. PMID:26910849

  7. The 'Tully monster' is a vertebrate.

    PubMed

    McCoy, Victoria E; Saupe, Erin E; Lamsdell, James C; Tarhan, Lidya G; McMahon, Sean; Lidgard, Scott; Mayer, Paul; Whalen, Christopher D; Soriano, Carmen; Finney, Lydia; Vogt, Stefan; Clark, Elizabeth G; Anderson, Ross P; Petermann, Holger; Locatelli, Emma R; Briggs, Derek E G

    2016-04-28

    Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the 'problem of the problematica', particularly the 'weird wonders' of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium, popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans, polychaetes, gastropods, conodonts, and the stem arthropod Opabinia. Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes. We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys, a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years. PMID:26982721

  8. The 'Tully monster' is a vertebrate.

    PubMed

    McCoy, Victoria E; Saupe, Erin E; Lamsdell, James C; Tarhan, Lidya G; McMahon, Sean; Lidgard, Scott; Mayer, Paul; Whalen, Christopher D; Soriano, Carmen; Finney, Lydia; Vogt, Stefan; Clark, Elizabeth G; Anderson, Ross P; Petermann, Holger; Locatelli, Emma R; Briggs, Derek E G

    2016-04-28

    Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the 'problem of the problematica', particularly the 'weird wonders' of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium, popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans, polychaetes, gastropods, conodonts, and the stem arthropod Opabinia. Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes. We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys, a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years.

  9. Frizzled-8 is expressed in the Spemann organizer and plays a role in early morphogenesis.

    PubMed

    Deardorff, M A; Tan, C; Conrad, L J; Klein, P S

    1998-07-01

    Wnts are secreted signaling molecules implicated in a large number of developmental processes. Frizzled proteins have been identified as likely receptors for Wnt ligands in vertebrates and invertebrates, but a functional role for vertebrate frizzleds has not yet been defined. To assess the endogenous role of frizzled proteins during vertebrate development, we have identified and characterized a Xenopus frizzled gene (xfz8). It is highly expressed in the deep cells of the Spemann organizer prior to dorsal lip formation and in the early involuting marginal zone. Ectopic expression of xfz8 in ventral cells leads to complete secondary axis formation and can synergize with Xwnt-8 while an inhibitory form of xfz8 (Nxfz8) blocks axis duplication by Xwnt-8, consistent with a role for xfz8 in Wnt signal transduction. Expression of Nxfz8 in dorsal cells has profound effects on morphogenesis during gastrulation and neurulation that result in dramatic shortening of the anterior-posterior axis. Our results suggest a role for xfz8 in morphogenesis during the gastrula stage of embryogenesis.

  10. Hemodynamics driven cardiac valve morphogenesis.

    PubMed

    Steed, Emily; Boselli, Francesco; Vermot, Julien

    2016-07-01

    Mechanical forces are instrumental to cardiovascular development and physiology. The heart beats approximately 2.6 billion times in a human lifetime and heart valves ensure that these contractions result in an efficient, unidirectional flow of the blood. Composed of endocardial cells (EdCs) and extracellular matrix (ECM), cardiac valves are among the most mechanically challenged structures of the body both during and after their development. Understanding how hemodynamic forces modulate cardiovascular function and morphogenesis is key to unraveling the relationship between normal and pathological cardiovascular development and physiology. Most valve diseases have their origins in embryogenesis, either as signs of abnormal developmental processes or the aberrant re-expression of fetal gene programs normally quiescent in adulthood. Here we review recent discoveries in the mechanobiology of cardiac valve development and introduce the latest technologies being developed in the zebrafish, including live cell imaging and optical technologies, as well as modeling approaches that are currently transforming this field. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  11. Vertex Models of Epithelial Morphogenesis

    PubMed Central

    Fletcher, Alexander G.; Osterfield, Miriam; Baker, Ruth E.; Shvartsman, Stanislav Y.

    2014-01-01

    The dynamic behavior of epithelial cell sheets plays a central role during numerous developmental processes. Genetic and imaging studies of epithelial morphogenesis in a wide range of organisms have led to increasingly detailed mechanisms of cell sheet dynamics. Computational models offer a useful means by which to investigate and test these mechanisms, and have played a key role in the study of cell-cell interactions. A variety of modeling approaches can be used to simulate the balance of forces within an epithelial sheet. Vertex models are a class of such models that consider cells as individual objects, approximated by two-dimensional polygons representing cellular interfaces, in which each vertex moves in response to forces due to growth, interfacial tension, and pressure within each cell. Vertex models are used to study cellular processes within epithelia, including cell motility, adhesion, mitosis, and delamination. This review summarizes how vertex models have been used to provide insight into developmental processes and highlights current challenges in this area, including progressing these models from two to three dimensions and developing new tools for model validation. PMID:24896108

  12. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype.

    PubMed

    Hirata, Hiroaki; Yurube, Takashi; Kakutani, Kenichiro; Maeno, Koichiro; Takada, Toru; Yamamoto, Junya; Kurakawa, Takuto; Akisue, Toshihiro; Kuroda, Ryosuke; Kurosaka, Masahiro; Nishida, Kotaro

    2014-03-01

    The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types-notochordal cells (NCs) and non-notochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2α-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration.

  13. Testing Skills in Vertebrates

    ERIC Educational Resources Information Center

    Funk, Mildred Sears; Tosto, Pat

    2007-01-01

    In this article, the authors present a project that gives students examples of basic skills that many vertebrate species develop as they grow and function in their ecosystem. These activities involve information gathering about surroundings, learning how to use objects, and tracking and searching skills. Different vertebrate species may acquire…

  14. NME genes in epithelial morphogenesis

    PubMed Central

    2012-01-01

    The NME family of genes encodes highly conserved multifunctional proteins that have been shown to participate in nucleic acid metabolism, energy homeostasis, cell signaling, and cancer progression. Some family members, particularly isoforms 1 and 2, have attracted extensive interests because of their potential anti-metastasis activity. Unfortunately, there have been few consensus mechanistic explanations for this critical function because of the numerous molecular functions ascribed to these proteins, including nucleoside diphosphate kinase, protein kinase, nuclease, transcription factor, growth factor, among others. In addition, different studies showed contradictory prognostic correlations between NME expression levels and tumor progression in clinical samples. Thus, analyses using pliable in vivo systems have become critical for unraveling at least some aspects of the complex functions of this family of genes. Recent works using the Drosophila genetic system have suggested a role for NME in regulating epithelial cell motility and morphogenesis, which has also been demonstrated in mammalian epithelial cell culture. This function is mediated by promoting internalization of growth factor receptors in motile epithelial cells, and the adherens junction components such as E-cadherin and β-catenin in epithelia that form the tissue linings. Interestingly, NME genes in epithelial cells appear to function in a defined range of expression levels. Either down-regulation or over-expression can perturb epithelial integrity, resulting in different aspects of epithelial abnormality. Such biphasic functions provide a plausible explanation for the documented anti-metastatic activity and the suspected oncogenic function. This review summarizes these recent findings and discusses their implications. PMID:21336542

  15. Atypical vertebral Paget's disease.

    PubMed

    Beaudouin, Constance; Dohan, Anthony; Nasrallah, Toufic; Parlier, Caroline; Touraine, Sébastien; Ea, Korng; Kaci, Rachid; Laredo, Jean-Denis

    2014-07-01

    A 40-year-old Mauritanian man consulted for back pain. A computed tomography of the spine showed patchy sclerosis of the fifth and seventh thoracic vertebral bodies with normal neural arch of T5 and sclerosis and hypertrophy of the neural arch of T7, as well as diffuse sclerosis of the T11 vertebral body with a normal neural arch. At MRI, low signal-intensity on T1-weighted images and high signal-intensity on T2-weighted images involved the whole T5 and T7 vertebrae and the vertebral body of T11. Working diagnoses included metastatic disease and lymphoma, and a biopsy of T7 and then T11 was carried out. Both showed pathological findings very suggestive of Paget's disease. Since CT is usually the more specific radiological examination in vertebral Paget's disease, we thought it could be useful to report this atypical CT presentation (patchy sclerosis of the vertebral body without diffuse bone texture changes and isolated involvement of the vertebral body) of vertebral Paget's disease. PMID:24445956

  16. Activation of autophagy via Ca2+-dependent AMPK/mTOR pathway in rat notochordal cells is a cellular adaptation under hyperosmotic stress

    PubMed Central

    Jiang, Li-Bo; Cao, Lu; Yin, Xiao-Fan; Yasen, Miersalijiang; Yishake, Mumingjiang; Dong, Jian; Li, Xi-Lei

    2015-01-01

    Nucleus pulposus (NP) cells experience hyperosmotic stress in spinal discs; however, how these cells can survive in the hostile microenvironment remains unclear. Autophagy has been suggested to maintain cellular homeostasis under different stresses by degrading the cytoplasmic proteins and organelles. Here, we explored whether autophagy is a cellular adaptation in rat notochordal cells under hyperosmotic stress. Hyperosmotic stress was found to activate autophagy in a dose- and time-dependent manner. SQSTM1/P62 expression was decreased as the autophagy level increased. Transient Ca2+ influx from intracellular stores and extracellular space was stimulated by hyperosmotic stress. Activation of AMPK and inhibition of p70S6K were observed under hyperosmotic conditions. However, intercellular Ca2+ chelation inhibited the increase of LC3-II and partly reversed the decrease of p70S6K. Hyperosmotic stress decreased cell viability and promoted apoptosis. Inhibition of autophagy led to SQSTM1/P62 accumulation, reduced cell viability, and accelerated apoptosis in notochordal cells under this condition. These evidences suggest that autophagy induction via the Ca2+-dependent AMPK/mTOR pathway might occur as an adaptation mechanism for notochordal cells under hyperosmotic stress. Thus, activating autophagy might be a promising approach to improve viability of notochordal cells in intervertebral discs. PMID:25590373

  17. FERM proteins in animal morphogenesis.

    PubMed

    Tepass, Ulrich

    2009-08-01

    Proteins containing a FERM domain are ubiquitous components of the cytocortex of animal cells where they are engaged in structural, transport, and signaling functions. Recent years have seen a wealth of genetic studies in model organisms that explore FERM protein function in development and tissue organization. In addition, mutations in several FERM protein-encoding genes have been associated with human diseases. This review will provide a brief overview of the FERM domain structure and the FERM protein superfamily and then discuss recent advances in our understanding of the mechanism of function and developmental requirement of several FERM proteins including Moesin, Myosin-VIIA, Myosin-XV, Coracle/Band4.1 as well as Yurt and its vertebrate homologs Mosaic Eyes and EPB41L5/YMO1/Limulus. PMID:19596566

  18. Extracellular matrix motion and early morphogenesis.

    PubMed

    Loganathan, Rajprasad; Rongish, Brenda J; Smith, Christopher M; Filla, Michael B; Czirok, Andras; Bénazéraf, Bertrand; Little, Charles D

    2016-06-15

    For over a century, embryologists who studied cellular motion in early amniotes generally assumed that morphogenetic movement reflected migration relative to a static extracellular matrix (ECM) scaffold. However, as we discuss in this Review, recent investigations reveal that the ECM is also moving during morphogenesis. Time-lapse studies show how convective tissue displacement patterns, as visualized by ECM markers, contribute to morphogenesis and organogenesis. Computational image analysis distinguishes between cell-autonomous (active) displacements and convection caused by large-scale (composite) tissue movements. Modern quantification of large-scale 'total' cellular motion and the accompanying ECM motion in the embryo demonstrates that a dynamic ECM is required for generation of the emergent motion patterns that drive amniote morphogenesis. PMID:27302396

  19. Extracellular matrix motion and early morphogenesis.

    PubMed

    Loganathan, Rajprasad; Rongish, Brenda J; Smith, Christopher M; Filla, Michael B; Czirok, Andras; Bénazéraf, Bertrand; Little, Charles D

    2016-06-15

    For over a century, embryologists who studied cellular motion in early amniotes generally assumed that morphogenetic movement reflected migration relative to a static extracellular matrix (ECM) scaffold. However, as we discuss in this Review, recent investigations reveal that the ECM is also moving during morphogenesis. Time-lapse studies show how convective tissue displacement patterns, as visualized by ECM markers, contribute to morphogenesis and organogenesis. Computational image analysis distinguishes between cell-autonomous (active) displacements and convection caused by large-scale (composite) tissue movements. Modern quantification of large-scale 'total' cellular motion and the accompanying ECM motion in the embryo demonstrates that a dynamic ECM is required for generation of the emergent motion patterns that drive amniote morphogenesis.

  20. Mechanics and morphogenesis of fission yeast cells.

    PubMed

    Davì, Valeria; Minc, Nicolas

    2015-12-01

    The integration of biochemical and biomechanical elements is at the heart of morphogenesis. While animal cells are relatively soft objects which shape and mechanics is mostly regulated by cytoskeletal networks, walled cells including those of plants, fungi and bacteria are encased in a rigid cell wall which resist high internal turgor pressure. How these particular mechanical properties may influence basic cellular processes, such as growth, shape and division remains poorly understood. Recent work using the model fungal cell fission yeast, Schizosaccharomyces pombe, highlights important contribution of cell mechanics to various morphogenesis processes. We envision this genetically tractable system to serve as a novel standard for the mechanobiology of walled cell.

  1. [Vertebral vacuum phenomena].

    PubMed

    Hamzé, B; Leaute, F; Wybier, M; Laredo, J D

    1995-01-01

    The spinal vacuum phenomenon is a collection of gas within the disk space, the vertebral body, the apophyseal joint or the spinal canal. The intradiscal vacuum phenomenon is frequently observed in degenerative disk disease and crystal-induced diskopathy. This has obvious significance to the radiologist, who, on observing a narrowed disk space or collapsed vertebral body, might otherwise consider infectious or neoplastic spondylitis, a likely possibility. The presence of vacuum phenomenon militates against the diagnosis of infection or tumor.

  2. Chordoma-derived cell line U-CH1-N recapitulates the biological properties of notochordal nucleus pulposus cells.

    PubMed

    Fujita, Nobuyuki; Suzuki, Satoshi; Watanabe, Kota; Ishii, Ken; Watanabe, Ryuichi; Shimoda, Masayuki; Takubo, Keiyo; Tsuji, Takashi; Toyama, Yoshiaki; Miyamoto, Takeshi; Horiuchi, Keisuke; Nakamura, Masaya; Matsumoto, Morio

    2016-08-01

    Intervertebral disc degeneration proceeds with age and is one of the major causes of lumbar pain and degenerative lumbar spine diseases. However, studies in the field of intervertebral disc biology have been hampered by the lack of reliable cell lines that can be used for in vitro assays. In this study, we show that a chordoma-derived cell line U-CH1-N cells highly express the nucleus pulposus (NP) marker genes, including T (encodes T brachyury transcription factor), KRT19, and CD24. These observations were further confirmed by immunocytochemistry and flow cytometry. Reporter analyses showed that transcriptional activity of T was enhanced in U-CH1-N cells. Chondrogenic capacity of U-CH1-N cells was verified by evaluating the expression of extracellular matrix (ECM) genes and Alcian blue staining. Of note, we found that proliferation and synthesis of chondrogenic ECM proteins were largely dependent on T in U-CH1-N cells. In accordance, knockdown of the T transcripts suppressed the expression of PCNA, a gene essential for DNA replication, and SOX5 and SOX6, the master regulators of chondrogenesis. On the other hand, the CD24-silenced cells showed no reduction in the mRNA expression level of the chondrogenic ECM genes. These results suggest that U-CH1-N shares important biological properties with notochordal NP cells and that T plays crucial roles in maintaining the notochordal NP cell-like phenotype in this cell line. Taken together, our data indicate that U-CH1-N may serve as a useful tool in studying the biology of intervertebral disc. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 34:1341-1350, 2016.

  3. Renal branching morphogenesis: morphogenetic and signaling mechanisms.

    PubMed

    Blake, Joshua; Rosenblum, Norman D

    2014-12-01

    The human kidney is composed of an arborized network of collecting ducts, calyces and urinary pelvis that facilitate urine excretion and regulate urine composition. The renal collecting system is formed in utero, completed by the 34th week of gestation in humans, and dictates final nephron complement. The renal collecting system arises from the ureteric bud, a derivative of the intermediate-mesoderm derived nephric duct that responds to inductive signals from adjacent tissues via a process termed ureteric induction. The ureteric bud subsequently undergoes a series of iterative branching and remodeling events in a process called renal branching morphogenesis. Altered signaling that disrupts patterning of the nephric duct, ureteric induction, or renal branching morphogenesis leads to varied malformations of the renal collecting system collectively known as congenital anomalies of the kidney and urinary tract (CAKUT) and is the most frequently detected congenital renal aberration in infants. Here, we describe critical morphogenetic and cellular events that govern nephric duct specification, ureteric bud induction, renal branching morphogenesis, and cessation of renal branching morphogenesis. We also highlight salient molecular signaling pathways that govern these processes, and the investigative techniques used to interrogate them. PMID:25080023

  4. Failure of articular process (zygaphophyseal) joint development as a cause of vertebral fusion (blocked vertebrae).

    PubMed Central

    Chandraraj, S

    1987-01-01

    Examination of congenitally fused (blocked) vertebrae in this study suggests that non-development of the joint between articular facets results in fusion of the vertebral arches which in turn leads to secondary fusion of the bodies and hypoplasia of the intervertebral discs. The presence of independent pedicles and transverse processes do not favour the concept that such an abnormality is the result of non-segmentation of the sclerotome. The condition is probably linked to a defect of an inductor substance which influences normal morphogenesis of the vertebral arch in the embryonic period. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:3429327

  5. Vertebrate Intestinal Endoderm Development

    PubMed Central

    Spence, Jason R.; Lauf, Ryan; Shroyer, Noah F.

    2010-01-01

    The endoderm gives rise to the lining of the esophagus, stomach and intestines, as well as associated organs. To generate a functional intestine, a series of highly orchestrated developmental processes must occur. In this review, we attempt to cover major events during intestinal development from gastrulation to birth, including endoderm formation, gut tube growth and patterning, intestinal morphogenesis, epithelial reorganization, villus emergence as well as proliferation and cytodifferentiation. Our discussion includes morphological and anatomical changes during intestinal development as well as molecular mechanisms regulating these processes. PMID:21246663

  6. Evolution of vertebrate mechanosensory hair cells and inner ears: toward identifying stimuli that select mutation driven altered morphologies

    PubMed Central

    Fritzsch, Bernd; Straka, Hans

    2014-01-01

    Among the major distance senses of vertebrates, the ear is unique in its complex morphological changes during evolution. Conceivably, these changes enable the ear to adapt toward sensing various physically well-characterized stimuli. This review develops a scenario that integrates sensory cell with organ evolution. We propose that molecular and cellular evolution of the vertebrate hair cells occurred prior to the formation of the vertebrate ear. We previously proposed that the genes driving hair cell differentiation, were aggregated in the otic region through developmental re-patterning that generated a unique vertebrate embryonic structure, the otic placode. In agreement with the presence of graviceptive receptors in many vertebrate outgroups, it is likely that the vertebrate ear originally functioned as a simple gravity-sensing organ. Based on the rare occurrence of angular acceleration receptors in vertebrate outgroups, we further propose that the canal system evolved with a more sophisticated ear morphogenesis. This evolving morphogenesis obviously turned the initial otocyst into a complex set of canals and recesses, harboring multiple sensory epithelia each adapted to the acquisition of a specific aspect of a given physical stimulus. As support for this evolutionary progression, we provide several details of the molecular basis of ear development. PMID:24281353

  7. Osteoporotic vertebral fractures redux.

    PubMed

    Lentle, B C; Gordon, P; Ward, L

    2008-02-01

    Osteoporosis remains an important cause of morbidity and mortality especially in the elderly. This fact is largely due to fractures of the proximal femur and spine. As recently recognized, vertebral fractures are as much a threat to health and longevity as fractures of the proximal femur. In recent decades, the development of tools to evaluate fracture risk as well as medications to treat osteoporosis has altered the management of people who are at fracture risk. At the same time identification and management procedures concerning spinal fracturing are not very clear. Besides there is not even clear consensus about what exactly constitutes a vertebral fracture, particularly those of minor degree. While height loss is a simple and valuable tool to detect vertebral fractures, it is neither sensitive nor specific enough to replace radiographs. Some 65% of fractures cause no symptoms. Often vertebral fractures are misdiagnosed, especially if they have occurred silently and if the opportunity for diagnosis arises fortuitously. It is to the patient's benefit that radiologists report and physicians identify vertebral fractures evident on a chest or other radiograph, no matter how incidental to the immediate clinical indication for the examination. Technological evolution now allows dual-energy x-ray absorptiometry machines to be used to take spine images while doing a densitometry. The images are adequate, even if not of high radiographic quality, and, more important, the patient undergoes a smaller radiation dose than with conventional spinal radiographs. Such technology may promote fracture recognition. The recognition of vertebral fractures, as well as the prevention and treatment of further fractures, will likely do much to reduce both the burden of osteoporosis-related morbidity and mortality, as well as fracture-related costs to healthcare systems.

  8. Computational Models for Mechanics of Morphogenesis

    PubMed Central

    Wyczalkowski, Matthew A.; Chen, Zi; Filas, Benjamen A.; Varner, Victor D.; Taber, Larry A.

    2012-01-01

    In the developing embryo, tissues differentiate, deform, and move in an orchestrated manner to generate various biological shapes driven by the complex interplay between genetic, epigenetic, and environmental factors. Mechanics plays a key role in regulating and controlling morphogenesis, and quantitative models help us understand how various mechanical forces combine to shape the embryo. Models allow for the quantitative, unbiased testing of physical mechanisms, and when used appropriately, can motivate new experimental directions. This knowledge benefits biomedical researchers who aim to prevent and treat congenital malformations, as well as engineers working to create replacement tissues in the laboratory. In this review, we first give an overview of fundamental mechanical theories for morphogenesis, and then focus on models for specific processes, including pattern formation, gastrulation, neurulation, organogenesis, and wound healing. The role of mechanical feedback in development is also discussed. Finally, some perspectives are given on the emerging challenges in morphomechanics and mechanobiology. PMID:22692887

  9. Imaging morphogenesis: technological advances and biological insights.

    PubMed

    Keller, Philipp J

    2013-06-01

    Morphogenesis, the development of the shape of an organism, is a dynamic process on a multitude of scales, from fast subcellular rearrangements and cell movements to slow structural changes at the whole-organism level. Live-imaging approaches based on light microscopy reveal the intricate dynamics of this process and are thus indispensable for investigating the underlying mechanisms. This Review discusses emerging imaging techniques that can record morphogenesis at temporal scales from seconds to days and at spatial scales from hundreds of nanometers to several millimeters. To unlock their full potential, these methods need to be matched with new computational approaches and physical models that help convert highly complex image data sets into biological insights.

  10. Feedback, Lineages and Self-Organizing Morphogenesis

    PubMed Central

    Calof, Anne L.; Lowengrub, John S.; Lander, Arthur D.

    2016-01-01

    Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities. PMID:26989903

  11. [Morphogenesis in a community of filamentous cyanobacteria].

    PubMed

    Sumina, E L; Sumin, D L

    2013-01-01

    Reversible differentiation was experimentally discovered in a community of modern filamentous cyanobacteria Oscillatoria terebriformis. Splitting of the initially uniform community into differentiated parts (strands, multiradiate aggregates, networks, etc.) occurs only for the duration of a function facilitating the activity of this community as an integral unit. The structures are formed as a result of regrouping of the filaments, without their specialization. A morphologically regulatory system (polygonal network) was found to develop under the impact of extreme factors. The levels of structural organization of filamentous cyanobacteria and multicellular eukaryotes were compared (individual cells in a filament--cell organelles; filaments--individual cells; community--organism), and the similarities and differences in morphogenesis of these groups were analyzed using the data on the embryonic regulation in multicellular eukaryotes. Spatial information in morphogenesis was shown to result not from direct realization of an inherited program but is created by the elements of integral organisms (cells and filaments) in the course of development.

  12. Feedback, Lineages and Self-Organizing Morphogenesis.

    PubMed

    Kunche, Sameeran; Yan, Huaming; Calof, Anne L; Lowengrub, John S; Lander, Arthur D

    2016-03-01

    Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities. PMID:26989903

  13. Multiparametric Image Analysis of Lung Branching Morphogenesis

    PubMed Central

    Schnatwinkel, Carsten; Niswander, Lee

    2013-01-01

    BACKGROUND Lung branching morphogenesis is a fundamental developmental process, yet the cellular dynamics that occur during lung development and the molecular mechanisms underlying recent postulated branching modes are poorly understood. RESULTS Here, we implemented a time-lapse video microscopy method to study the cellular behavior and molecular mechanisms of planar bifurcation and domain branching in lung explant- and organotypic cultures. Our analysis revealed morphologically distinct stages that are shaped at least in part by a combination of localized and orientated cell divisions and by local mechanical forces. We also identified myosin light-chain kinase as an important regulator of bud bifurcation, but not domain branching in lung explants. CONCLUSION This live imaging approach provides a method to study cellular behavior during lung branching morphogenesis and suggests the importance of a mechanism primarily based on oriented cell proliferation and mechanical forces in forming and shaping the developing lung airways. PMID:23483685

  14. Peripheral nerve morphogenesis induced by scaffold micropatterning

    PubMed Central

    Memon, Danish; Boneschi, Filippo Martinelli; Madaghiele, Marta; Brambilla, Paola; Del Carro, Ubaldo; Taveggia, Carla; Riva, Nilo; Trimarco, Amelia; Lopez, Ignazio D.; Comi, Giancarlo; Pluchino, Stefano; Martino, Gianvito; Sannino, Alessandro; Quattrini, Angelo

    2014-01-01

    Several bioengineering approaches have been proposed for peripheral nervous system repair, with limited results and still open questions about the underlying molecular mechanisms. We assessed the biological processes that occur after the implantation of collagen scaffold with a peculiar porous microstructure of the wall in a rat sciatic nerve transection model compared to commercial collagen conduits and nerve crush injury using functional, histological and genome wide analyses. We demonstrated that within 60 days, our conduit had been completely substituted by a normal nerve. Gene expression analysis documented a precise sequential regulation of known genes involved in angiogenesis, Schwann cells/axons interactions and myelination, together with a selective modulation of key biological pathways for nerve morphogenesis induced by porous matrices. These data suggest that the scaffold’s microstructure profoundly influences cell behaviors and creates an instructive micro-environment to enhance nerve morphogenesis that can be exploited to improve recovery and understand the molecular differences between repair and regeneration. PMID:24559639

  15. Punctuated evolution and robustness in morphogenesis

    PubMed Central

    Grigoriev, D.; Reinitz, J.; Vakulenko, S.; Weber, A.

    2014-01-01

    This paper presents an analytic approach to the pattern stability and evolution problem in morphogenesis. The approach used here is based on the ideas from the gene and neural network theory. We assume that gene networks contain a number of small groups of genes (called hubs) controlling morphogenesis process. Hub genes represent an important element of gene network architecture and their existence is empirically confirmed. We show that hubs can stabilize morphogenetic pattern and accelerate the morphogenesis. The hub activity exhibits an abrupt change depending on the mutation frequency. When the mutation frequency is small, these hubs suppress all mutations and gene product concentrations do not change, thus, the pattern is stable. When the environmental pressure increases and the population needs new genotypes, the genetic drift and other effects increase the mutation frequency. For the frequencies that are larger than a critical amount the hubs turn off; and as a result, many mutations can affect phenotype. This effect can serve as an engine for evolution. We show that this engine is very effective: the evolution acceleration is an exponential function of gene redundancy. Finally, we show that the Eldredge-Gould concept of punctuated evolution results from the network architecture, which provides fast evolution, control of evolvability, and pattern robustness. To describe analytically the effect of exponential acceleration, we use mathematical methods developed recently for hard combinatorial problems, in particular, for so-called k-SAT problem, and numerical simulations. PMID:24996115

  16. ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish

    PubMed Central

    Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L.; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi

    2013-01-01

    ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra. PMID:23447699

  17. Management of osteoporotic vertebral fractures

    PubMed Central

    Dionyssiotis, Yannis

    2010-01-01

    Osteoporotic vertebral fractures are associated with considerable reduction of quality of life, morbidity, and mortality. The management of patients with vertebral fractures should include treatment for osteoporosis and measures to reduce pain and improve mobility. This article provides information for management and rehabilitation of vertebral fractures based on clinical experience and literature. PMID:20689689

  18. Evolution and development of the vertebrate ear

    NASA Technical Reports Server (NTRS)

    Fritzsch, B.; Beisel, K. W.

    2001-01-01

    This review outlines major aspects of development and evolution of the ear, specifically addressing issues of cell fate commitment and the emerging molecular governance of these decisions. Available data support the notion of homology of subsets of mechanosensors across phyla (proprioreceptive mechanosensory neurons in insects, hair cells in vertebrates). It is argued that this conservation is primarily related to the specific transducing environment needed to achieve mechanosensation. Achieving this requires highly conserved transcription factors that regulate the expression of the relevant structural genes for mechanosensory transduction. While conserved at the level of some cell fate assignment genes (atonal and its mammalian homologue), the ear has also radically reorganized its development by implementing genes used for cell fate assignment in other parts of the developing nervous systems (e.g., neurogenin 1) and by evolving novel sets of genes specifically associated with the novel formation of sensory neurons that contact hair cells (neurotrophins and their receptors). Numerous genes have been identified that regulate morphogenesis, but there is only one common feature that emerges at the moment: the ear appears to have co-opted genes from a large variety of other parts of the developing body (forebrain, limbs, kidneys) and establishes, in combination with existing transcription factors, an environment in which those genes govern novel, ear-related morphogenetic aspects. The ear thus represents a unique mix of highly conserved developmental elements combined with co-opted and newly evolved developmental elements.

  19. Head segmentation in vertebrates

    PubMed Central

    Kuratani, Shigeru; Schilling, Thomas

    2008-01-01

    Classic theories of vertebrate head segmentation clearly exemplify the idealistic nature of comparative embryology prior to the 20th century. Comparative embryology aimed at recognizing the basic, primary structure that is shared by all vertebrates, either as an archetype or an ancestral developmental pattern. Modern evolutionary developmental (Evo-Devo) studies are also based on comparison, and therefore have a tendency to reduce complex embryonic anatomy into overly simplified patterns. Here again, a basic segmental plan for the head has been sought among chordates. We convened a symposium that brought together leading researchers dealing with this problem, in a number of different evolutionary and developmental contexts. Here we give an overview of the outcome and the status of the field in this modern era of Evo-Devo. We emphasize the fact that the head segmentation problem is not fully resolved, and we discuss new directions in the search for hints for a way out of this maze. PMID:20607135

  20. [Vertebral hydatidosis: case report].

    PubMed

    Varela, R; Santelices, J P; Cuzmar, D; Aldunate, J T; Plaza-Guzmán, N; Lizama-Calvo, P

    2015-01-01

    Hydatidosis caused by echinococcus granulosus may affect any organ in the body, with the lungs and the liver as the most commonly affected organs. Vertebral compromise resulting from echinococcus granulosus has a low prevalence and accounts for less than 1% of bone compromise. We report the case of a 50 year-old female who presented at the Trauma Service with progressive low back pain with 5 months of duration that irradiated to the right lower limb, and led to neurologic compromise of the limb. Imaging studies showed spondylodiscitis at T12-L1, confirmed by a biopsy. Treatment of this condition is both orthopedic and surgical. The recurrence rate is high, between 30 and 40%. The objective of describing this case is to propose the differential diagnosis of a vertebral mass of unknown origin and provide details as to how to manage this condition. PMID:27012085

  1. Viruses of lower vertebrates.

    PubMed

    Essbauer, S; Ahne, W

    2001-08-01

    Viruses of lower vertebrates recently became a field of interest to the public due to increasing epizootics and economic losses of poikilothermic animals. These were reported worldwide from both wildlife and collections of aquatic poikilothermic animals. Several RNA and DNA viruses infecting fish, amphibians and reptiles have been studied intensively during the last 20 years. Many of these viruses induce diseases resulting in important economic losses of lower vertebrates, especially in fish aquaculture. In addition, some of the DNA viruses seem to be emerging pathogens involved in the worldwide decline in wildlife. Irido-, herpes- and polyomavirus infections may be involved in the reduction in the numbers of endangered amphibian and reptile species. In this context the knowledge of several important RNA viruses such as orthomyxo-, paramyxo-, rhabdo-, retro-, corona-, calici-, toga-, picorna-, noda-, reo- and birnaviruses, and DNA viruses such as parvo-, irido-, herpes-, adeno-, polyoma- and poxviruses, is described in this review. PMID:11550762

  2. Building the Vertebrate Spine

    NASA Astrophysics Data System (ADS)

    Pourquié, Olivier

    2008-03-01

    The vertebrate body can be subdivided along the antero-posterior (AP) axis into repeated structures called segments. This periodic pattern is established during embryogenesis by the somitogenesis process. Somites are generated in a rhythmic fashion from the paraxial mesoderm and subsequently differentiate to give rise to the vertebrae and skeletal muscles of the body. Somite formation involves an oscillator-the segmentation clock-whose periodic signal is converted into the periodic array of somite boundaries. This clock drives the dynamic expression of cyclic genes in the presomitic mesoderm and requires Notch and Wnt signaling. Microarray studies of the mouse presomitic mesoderm transcriptome reveal that the segmentation clock drives the periodic expression of a large network of cyclic genes involved in cell signaling. Mutually exclusive activation of the Notch/FGF and Wnt pathways during each cycle suggests that coordinated regulation of these three pathways underlies the clock oscillator. In humans, mutations in the genes associated to the function of this oscillator such as Dll3 or Lunatic Fringe result in abnormal segmentation of the vertebral column such as those seen in congenital scoliosis. Whereas the segmentation clock is thought to set the pace of vertebrate segmentation, the translation of this pulsation into the reiterated arrangement of segment boundaries along the AP axis involves dynamic gradients of FGF and Wnt signaling. The FGF signaling gradient is established based on an unusual mechanism involving mRNA decay which provides an efficient means to couple the spatio-temporal activation of segmentation to the posterior elongation of the embryo. Another striking aspect of somite production is the strict bilateral symmetry of the process. Retinoic acid was shown to control aspects of this coordination by buffering destabilizing effects from the embryonic left-right machinery. Defects in this embryonic program controlling vertebral symmetry might lead

  3. Intracardiac flow dynamics regulate atrioventricular valve morphogenesis

    PubMed Central

    Kalogirou, Stamatia; Malissovas, Nikos; Moro, Enrico; Argenton, Francesco; Stainier, Didier Y.R.; Beis, Dimitris

    2014-01-01

    Aims Valvular heart disease is responsible for considerable morbidity and mortality. Cardiac valves develop as the heart contracts, and they function throughout the lifetime of the organism to prevent retrograde blood flow. Their precise morphogenesis is crucial for cardiac function. Zebrafish is an ideal model to investigate cardiac valve development as it allows these studies to be carried out in vivo through non-invasive imaging. Accumulating evidence suggests a role for contractility and intracardiac flow dynamics in cardiac valve development. However, these two factors have proved difficult to uncouple, especially since altering myocardial function affects the intracardiac flow pattern. Methods and results Here, we describe novel zebrafish models of developmental valve defects. We identified two mutant alleles of myosin heavy chain 6 that can be raised to adulthood despite having only one functional chamber—the ventricle. The adult mutant ventricle undergoes remodelling, and the atrioventricular (AV) valves fail to form four cuspids. In parallel, we characterized a novel mutant allele of southpaw, a nodal-related gene involved in the establishment of left–right asymmetry, which exhibits randomized heart and endoderm positioning. We first observed that in southpaw mutants the relative position of the two cardiac chambers is altered, affecting the geometry of the heart, while myocardial function appears unaffected. Mutant hearts that loop properly or exhibit situs inversus develop normally, whereas midline, unlooped hearts exhibit defects in their transvalvular flow pattern during AV valve development as well as defects in valve morphogenesis. Conclusion Our data indicate that intracardiac flow dynamics regulate valve morphogenesis independently of myocardial contractility. PMID:25100766

  4. Morphogenesis of Venezuelan Equine Encephalomyelitis Virus

    PubMed Central

    Bykovsky, A. F.; Yershov, F. I.; Zhdanov, V. M.

    1969-01-01

    Morphogenesis of Venezuelan equine encephalomyelitis virus was studied by means of electron microscopy. Virus-specific structures (factories, viroplasts) were found at early stages of infection; these structures were composed of fibrillar and cylindrical formations, aggregates of ribosomes, and viral nucleoids. The latter emerged from fibrillar and cylindrical structures. Aggregates of viral nucleoids were found in the cytoplasm and occasionally in the nuclei of virus-infected cells. Viral envelopes and mature virions were formed on the cell membranes and on the membranes of intracellular vacuoles. Anomalous forms of virions (both polygenomic and oligogenomic) were observed. Images PMID:5823233

  5. Bidirectional extracellular matrix signaling during tissue morphogenesis

    PubMed Central

    Gjorevski, Nikolce; Nelson, Celeste M.

    2009-01-01

    Normal tissue development and function are regulated by the interplay between cells and their surrounding extracellular matrix (ECM). The ECM provides biochemical and mechanical contextual information that is conveyed from the cell membrane through the cytoskeleton to the nucleus to direct cell phenotype. Cells, in turn, remodel the ECM and thereby sculpt their local microenvironment. Here we review the mechanisms by which cells interact with, respond to, and influence the ECM, with particular emphasis placed on the role of this bidirectional communication during tissue morphogenesis. We also discuss the implications for successful engineering of functional tissues ex vivo. PMID:19896886

  6. Heterotypic control of basement membrane dynamics during branching morphogenesis.

    PubMed

    Nelson, Deirdre A; Larsen, Melinda

    2015-05-01

    Many mammalian organs undergo branching morphogenesis to create highly arborized structures with maximized surface area for specialized organ function. Cooperative cell-cell and cell-matrix adhesions that sculpt the emerging tissue architecture are guided by dynamic basement membranes. Properties of the basement membrane are reciprocally controlled by the interacting epithelial and mesenchymal cell populations. Here we discuss how basement membrane remodeling is required for branching morphogenesis to regulate cell-matrix and cell-cell adhesions that are required for cell patterning during morphogenesis and how basement membrane impacts morphogenesis by stimulation of cell patterning, force generation, and mechanotransduction. We suggest that in addition to creating mature epithelial architecture, remodeling of the epithelial basement membrane during branching morphogenesis is also essential to promote maturation of the stromal mesenchyme to create mature organ structure. Recapitulation of developmental cell-matrix and cell-cell interactions are of critical importance in tissue engineering and regeneration strategies that seek to restore organ function.

  7. Ernest Everett Just, Johannes Holtfreter, and the Origin of Certain Concepts in Embryo Morphogenesis

    PubMed Central

    BYRNES, W. MALCOLM

    2012-01-01

    SUMMARY Ernest E. Just (1883–1941) is best known for his discovery of the “wave of negativity” that sweeps of the sea urchin egg during fertilization, and his elucidation of what are known as the fast and slow blocks to polyspermy. Just’s contemporary Johannes Holtfreter (1901–1992) is known for his pioneering work in amphibian morphogenesis, which helped to lay the foundation for modern vertebrate developmental biology. This paper, after briefly describing the life and scientific contributions of Just, argues that his work and ideas strongly influenced two of the concepts for which Holtfreter is best known: tissue affinity and autoneuralization (or autoinduction). Specifically, this paper argues that, first, Just’s experiments demonstrating developmental stage-specific changes in the adhesiveness of the blastomeres of cleavage embryos helped lay the foundation for Holtfreter’s concept of tissue affinity and, second, Just’s notion of the intrinsic irritability of the egg cell, which is evident in experimental parthenogenesis, strongly informed Holtfreter’s concept of the nonspecific induction of neural tissue formation in amphibian gastrula ectoderm explants, a phenomenon known as auto-induction. Acknowledgment of these contributions by Just in no way diminishes the importance of Holtfreter’s groundbreaking work. It does, however, extend the impact of Just’s work into the area of embryo morphogenesis. It connects Just to Holtfreter and positions his work as an antecedent to embryo research that continues to this day. PMID:19610071

  8. Role of the Polycystins in Cell Migration, Polarity, and Tissue Morphogenesis

    PubMed Central

    Nigro, Elisa Agnese; Castelli, Maddalena; Boletta, Alessandra

    2015-01-01

    Cystic kidney diseases (CKD) is a class of disorders characterized by ciliary dysfunction and, therefore, belonging to the ciliopathies. The prototype CKD is autosomal dominant polycystic kidney disease (ADPKD), whose mutated genes encode for two membrane-bound proteins, polycystin-1 (PC-1) and polycystin-2 (PC-2), of unknown function. Recent studies on CKD-associated genes identified new mechanisms of morphogenesis that are central for establishment and maintenance of proper renal tubular diameter. During embryonic development in the mouse and lower vertebrates a convergent-extension (CE)-like mechanism based on planar cell polarity (PCP) and cellular intercalation is involved in “sculpting” the tubules into a narrow and elongated shape. Once the appropriate diameter is established, further elongation occurs through oriented cell division (OCD). The polycystins (PCs) regulate some of these essential processes. In this review we summarize recent work on the role of PCs in regulating cell migration, the cytoskeleton, and front-rear polarity. These important properties are essential for proper morphogenesis of the renal tubules and the lymphatic vessels. We highlight here several open questions and controversies. Finally, we try to outline some of the next steps required to study these processes and their relevance in physiological and pathological conditions. PMID:26529018

  9. Regulating Craniofacial Development at the 3' End: MicroRNAs and Their Function in Facial Morphogenesis.

    PubMed

    Tavares, Andre L P; Artinger, Kristin B; Clouthier, David E

    2015-01-01

    Defects in craniofacial development represent a majority of observed human birth defects, occurring at a rate as high as 1:800 live births. These defects often occur due to changes in neural crest cell (NCC) patterning and development and can affect non-NCC-derived structures due to interactions between NCCs and the surrounding cell types. Proper craniofacial development requires an intricate array of gene expression networks that are tightly controlled spatiotemporally by a number of regulatory mechanisms. One of these mechanisms involves the action of microRNAs (miRNAs), a class of noncoding RNAs that repress gene expression by binding to miRNA recognition sequences typically located in the 3' UTR of target mRNAs. Recent evidence illustrates that miRNAs are crucial for vertebrate facial morphogenesis, with changes in miRNA expression leading to facial birth defects, including some in complex human syndromes such as 22q11 (DiGeorge Syndrome). In this review, we highlight the current understanding of miRNA biogenesis, the roles of miRNAs in overall craniofacial development, the impact that loss of miRNAs has on normal development and the requirement for miRNAs in the development of specific craniofacial structures, including teeth. From these studies, it is clear that miRNAs are essential for normal facial development and morphogenesis, and a potential key in establishing new paradigms for repair and regeneration of facial defects. PMID:26589932

  10. Sensory roles of neuronal cilia: cilia development, morphogenesis, and function in C. elegans.

    PubMed

    Bae, Young-Kyung; Barr, Maureen M

    2008-01-01

    In the free-living nematode Caenorhabditis elegans, cilia are found on the dendritic endings of sensory neurons. C. elegans cilia are classified as 'primary' or 'sensory' according to the '9+0' axonemal ultrastructure (nine doublet outer microtubules with no central microtubule pair) and lack of motility, characteristics of '9+2' cilia. The C. elegans ciliated nervous system allows the animal to perceive environmental stimuli and make appropriate developmental, physiological, and behavioral decisions. In vertebrates, the biological significance of primary cilia had been largely neglected. Recent findings have placed primary/sensory cilia in the center of cellular signaling and developmental processes. Studies using genetic model organisms such as C. elegans identified the link between ciliary dysfunction and human ciliopathies. Future studies in the worm will address important basic questions regarding ciliary development, morphogenesis, specialization, and signaling functions. PMID:18508635

  11. Apical constriction: themes and variations on a cellular mechanism driving morphogenesis

    PubMed Central

    Martin, Adam C.; Goldstein, Bob

    2014-01-01

    Apical constriction is a cell shape change that promotes tissue remodeling in a variety of homeostatic and developmental contexts, including gastrulation in many organisms and neural tube formation in vertebrates. In recent years, progress has been made towards understanding how the distinct cell biological processes that together drive apical constriction are coordinated. These processes include the contraction of actin-myosin networks, which generates force, and the attachment of actin networks to cell-cell junctions, which allows forces to be transmitted between cells. Different cell types regulate contractility and adhesion in unique ways, resulting in apical constriction with varying dynamics and subcellular organizations, as well as a variety of resulting tissue shape changes. Understanding both the common themes and the variations in apical constriction mechanisms promises to provide insight into the mechanics that underlie tissue morphogenesis. PMID:24803648

  12. Soluble and pelletable factors in porcine, canine and human notochordal cell-conditioned medium: implications for IVD regeneration.

    PubMed

    Bach, F C; de Vries, S A; Riemers, F M; Boere, J; van Heel, F W; van Doeselaar, M; Goerdaya, S S; Nikkels, P G; Benz, K; Creemers, L B; Maarten Altelaar, A F; Meij, B P; Ito, K; Tryfonidou, M A

    2016-01-01

    During intervertebral disc (IVD) maturation, notochordal cells (NCs) are replaced by chondrocyte-like cells (CLCs) in the nucleus pulposus, suggesting that NCs play a role in maintaining tissue health. Affirmatively, NC-conditioned medium (NCCM) exerts regenerative effects on CLC proliferation and extracellular matrix (ECM) production. The aim of this study was to identify NC-secreted substances that stimulate IVD regeneration. By mass spectrometry of porcine, canine and human NCCM, 149, 170 and 217 proteins were identified, respectively, with 66 proteins in common. Mainly ECM-related proteins were identified, but also organelle-derived and membrane-bound vesicle proteins. To determine whether the effect of NCCM was mediated by soluble and/or pelletable factors, porcine and canine NCCM were separated into a soluble (NCCM-S; peptides and proteins) and pelletable (NCCM-P; protein aggregates and extracellular vesicles) fraction by ultracentrifugation, and tested on bovine and canine CLCs in vitro, respectively. In each model, NCCM-S exerted a more pronounced anabolic effect than NCCM-P. However, glycosaminoglycan (GAG) uptake from the medium into the carrier gel prevented more definite conclusions. While the effect of porcine NCCM-P on bovine CLCs was negligible, canine NCCM-P appeared to enhance GAG and collagen type II deposition by canine CLCs. In conclusion, porcine and canine NCCM exerted their anabolic effects mainly through soluble factors, but also the pelletable NCCM factors showed moderate regenerative potential. Although the regenerative potential of NCCM-P should not be overlooked, future studies should focus on unraveling the protein-based regenerative mechanism from NCCM produced from isolated NCs, e.g. by NCCM fractionation and pathway blocking studies. PMID:27572543

  13. Regional variation in morphology of vertebral centra and intervertebral joints in striped bass, Morone saxatilis.

    PubMed

    Nowroozi, B N; Harper, C J; De Kegel, B; Adriaens, D; Brainerd, E L

    2012-04-01

    The vertebral column of fishes has traditionally been divided into just two distinct regions, abdominal and caudal. Recently, however, developmental, morphological, and mechanical investigations have brought this traditional regionalization scheme into question. Alternative regionalization schema advocate the division of the abdominal vertebrae into cervical, abdominal, and in some cases, transitional regions. Here, we investigate regional variation at the level of the vertebrae and intervertebral joint (IVJ) tissues in the striped bass, Morone saxatilis. We use gross dissection, histology, and polarized light imaging to quantify vertebral height, width, length, IVJ length, IVJ tissue volume and cross-sectional area, and vertical septum fiber populations, and angles of insertion. Our results reveal regional differences between the first four (most rostral) abdominal vertebrae and IVJs and the next six abdominal vertebrae and IVJs, supporting the recognition of a distinct cervical region. We found significant variation in vertebral length, width, and height from cranial to caudal. In addition, we see a significant decline in the volume of notochordal cells and the cross-sectional area of the fibrous sheath from cranial to caudal. Further, polarized light imaging revealed four distinct fiber populations within the vertical septum in the cervical and abdominal regions in contrast with just one fiber population found in the caudal region. Measurement of the insertion angles of these fiber populations revealed significant differences between the cervical and abdominal regions. Differences in vertebral, IVJ, and vertical septum morphology all predict greater range of motion and decreased stiffness in the caudal region of the fish compared with the cervical and abdominal regions. PMID:22109664

  14. Regional variation in morphology of vertebral centra and intervertebral joints in striped bass, Morone saxatilis.

    PubMed

    Nowroozi, B N; Harper, C J; De Kegel, B; Adriaens, D; Brainerd, E L

    2012-04-01

    The vertebral column of fishes has traditionally been divided into just two distinct regions, abdominal and caudal. Recently, however, developmental, morphological, and mechanical investigations have brought this traditional regionalization scheme into question. Alternative regionalization schema advocate the division of the abdominal vertebrae into cervical, abdominal, and in some cases, transitional regions. Here, we investigate regional variation at the level of the vertebrae and intervertebral joint (IVJ) tissues in the striped bass, Morone saxatilis. We use gross dissection, histology, and polarized light imaging to quantify vertebral height, width, length, IVJ length, IVJ tissue volume and cross-sectional area, and vertical septum fiber populations, and angles of insertion. Our results reveal regional differences between the first four (most rostral) abdominal vertebrae and IVJs and the next six abdominal vertebrae and IVJs, supporting the recognition of a distinct cervical region. We found significant variation in vertebral length, width, and height from cranial to caudal. In addition, we see a significant decline in the volume of notochordal cells and the cross-sectional area of the fibrous sheath from cranial to caudal. Further, polarized light imaging revealed four distinct fiber populations within the vertical septum in the cervical and abdominal regions in contrast with just one fiber population found in the caudal region. Measurement of the insertion angles of these fiber populations revealed significant differences between the cervical and abdominal regions. Differences in vertebral, IVJ, and vertical septum morphology all predict greater range of motion and decreased stiffness in the caudal region of the fish compared with the cervical and abdominal regions.

  15. The differentiation and morphogenesis of craniofacial muscles.

    PubMed

    Noden, Drew M; Francis-West, Philippa

    2006-05-01

    Unraveling the complex tissue interactions necessary to generate the structural and functional diversity present among craniofacial muscles is challenging. These muscles initiate their development within a mesenchymal population bounded by the brain, pharyngeal endoderm, surface ectoderm, and neural crest cells. This set of spatial relations, and in particular the segmental properties of these adjacent tissues, are unique to the head. Additionally, the lack of early epithelialization in head mesoderm necessitates strategies for generating discrete myogenic foci that may differ from those operating in the trunk. Molecular data indeed indicate dissimilar methods of regulation, yet transplantation studies suggest that some head and trunk myogenic populations are interchangeable. The first goal of this review is to present key features of these diversities, identifying and comparing tissue and molecular interactions regulating myogenesis in the head and trunk. Our second focus is on the diverse morphogenetic movements exhibited by craniofacial muscles. Precursors of tongue muscles partly mimic migrations of appendicular myoblasts, whereas myoblasts destined to form extraocular muscles condense within paraxial mesoderm, then as large cohorts they cross the mesoderm:neural crest interface en route to periocular regions. Branchial muscle precursors exhibit yet another strategy, establishing contacts with neural crest populations before branchial arch formation and maintaining these relations through subsequent stages of morphogenesis. With many of the prerequisite stepping-stones in our knowledge of craniofacial myogenesis now in place, discovering the cellular and molecular interactions necessary to initiate and sustain the differentiation and morphogenesis of these neglected craniofacial muscles is now an attainable goal.

  16. Actomyosin stiffens the vertebrate embryo during crucial stages of elongation and neural tube closure

    PubMed Central

    Zhou, Jian; Kim, Hye Young; Davidson, Lance A.

    2009-01-01

    Summary Physical forces drive the movement of tissues within the early embryo. Classical and modern approaches have been used to infer and, in rare cases, measure mechanical properties and the location and magnitude of forces within embryos. Elongation of the dorsal axis is a crucial event in early vertebrate development, yet the mechanics of dorsal tissues in driving embryonic elongation that later support neural tube closure and formation of the central nervous system is not known. Among vertebrates, amphibian embryos allow complex physical manipulation of embryonic tissues that are required to measure the mechanical properties of tissues. In this paper, we measure the stiffness of dorsal isolate explants of frog (Xenopus laevis) from gastrulation to neurulation and find dorsal tissues stiffen from less than 20 Pascal (Pa) to over 80 Pa. By iteratively removing tissues from these explants, we find paraxial somitic mesoderm is nearly twice as stiff as either the notochord or neural plate, and at least 10-fold stiffer than the endoderm. Stiffness measurements from explants with reduced fibronectin fibril assembly or disrupted actomyosin contractility suggest that it is the state of the actomyosin cell cortex rather than accumulating fibronectin that controls tissue stiffness in early amphibian embryos. PMID:19168681

  17. Effects of Nd:YAG laser radiation in cultured porcine vertebral disc tissue

    NASA Astrophysics Data System (ADS)

    Thal, Dietmar R.; Werkmann, Klaus; Leheta, Fouad; Schober, Ralf; Ulrich, Peter

    1996-01-01

    Nd:Yag laser radiation is used for the treatment of protrusion of intervertebral discs. It is known that laser radiation leads to coagulation, vaporization and carbonization of the disk. Little is known about the early changes in vertebral discs after laser radiation. Therefore, we exposed cadaveric porcine vertebral discs by Nd:YAG laser radiation immediately after death. The discs were quartered and either formalin fixed after laser radiation or kept in culture for 1, 4 and 7 days and then formalin fixed. Immunohistochemistry was performed with antibodies directed against vimentin and amyloid precursor protein (APP). Results showed a jerky leak of notochordial remnant cells and mucopolysaccharides at the distal end of the application needle during laser radiation, which was interpreted as a bursting extrusion of damaged but not vaporized tissue. Histology and immunohistochemistry revealed an incomplete loss of nucleus pulposus and a large, almost complete necrosis of the notochordial remnant cells. In surviving notochordial remnant cells after laser radiation a slight increase of vimentin and APP could be seen without any other cellular reactions. The annulus fibrosus showed no significant changes except a defect with a small necrosis zone at the site of the application needle. Therefore, it can be concluded that Nd:YAG laser radiation leads to an increased volume reduction by the leak of nucleus pulposus and to a slight cellular reaction of surviving notochordal remnant cells detectable by vimentin and APP increase.

  18. Vertebrate Hedgehog is secreted on two types of extracellular vesicles with different signaling properties

    PubMed Central

    Vyas, Neha; Walvekar, Ankita; Tate, Dhananjay; Lakshmanan, Vairavan; Bansal, Dhiru; Cicero, Alessandra Lo; Raposo, Graca; Palakodeti, Dasaradhi; Dhawan, Jyotsna

    2014-01-01

    Hedgehog (Hh) is a secreted morphogen that elicits differentiation and patterning in developing tissues. Multiple proposed mechanisms to regulate Hh dispersion includes lipoprotein particles and exosomes. Here we report that vertebrate Sonic Hedgehog (Shh) is secreted on two types of extracellular-vesicles/exosomes, from human cell lines and primary chick notochord cells. Although largely overlapping in size as estimated from electron micrographs, the two exosomal fractions exhibited distinct protein and RNA composition. We have probed the functional properties of these vesicles using cell-based assays of Hh-elicited gene expression. Our results suggest that while both Shh-containing exo-vesicular fractions can activate an ectopic Gli-luciferase construct, only exosomes co-expressing Integrins can activate endogenous Shh target genes HNF3β and Olig2 during the differentiation of mouse ES cells to ventral neuronal progenitors. Taken together, our results demonstrate that primary vertebrate cells secrete Shh in distinct vesicular forms, and support a model where packaging of Shh along with other signaling proteins such as Integrins on exosomes modulates target gene activation. The existence of distinct classes of Shh-containing exosomes also suggests a previously unappreciated complexity for fine-tuning of Shh-mediated gradients and pattern formation. PMID:25483805

  19. Multifaceted roles of Furry proteins in invertebrates and vertebrates.

    PubMed

    Nagai, Tomoaki; Mizuno, Kensaku

    2014-03-01

    Furry (Fry) is a large protein that is evolutionarily conserved from yeast to human. Fry and its orthologues in invertebrates (termed Tao3p in budding yeast, Mor2p in fission yeast, Sax-2 in nematode and Fry in fruit fly) genetically and physically interact with nuclear Dbf2-related (NDR) kinases (termed Cbk1p in budding yeast, Orb6p in fission yeast, Sax-1 in nematode and Trc in fruitfly), and function as activators or scaffolds of these kinases. Fry-NDR kinase signals are implicated in the control of polarized cell growth and morphogenesis in yeast, neurite outgrowth in nematode, and epidermal morphogenesis and dendritic tiling in fruit fly. Recent studies revealed that mammalian Fry is a microtubule-associated protein that is involved in the control of chromosome alignment, spindle organization and Polo-like kinase-1 activation in mitosis, and promotes microtubule acetylation in mitotic spindles via inhibiting the tubulin deacetylase Sirtuin 2. Here, we review current knowledge about the diverse cellular functions and regulation of Fry proteins in invertebrates and vertebrates.

  20. Hox Genes and Regional Patterning of the Vertebrate Body Plan

    PubMed Central

    Mallo, Moises; Wellik, Deneen M.; Deschamps, Jacqueline

    2010-01-01

    Several decades have passed since the discovery of Hox genes in the fruit fly Drosophila melanogaster. Their unique ability to regulate morphologies along the anteroposterior (AP) axis (Lewis, 1978) earned them well-deserved attention as important regulators of embryonic development. Phenotypes due to loss- and gain-of-function mutations in mouse Hox genes have revealed that the spatiotemporally controlled expression of these genes is critical for the correct morphogenesis of embryonic axial structures. Here, we review recent novel insight into the modalities of Hox protein function in imparting specific identity to anatomical regions of the vertebral column, and in controlling the emergence of these tissues concomitantly with providing them with axial identity. The control of these functions must have been intimately linked to the shaping of the body plan during evolution. PMID:20435029

  1. The cellular and molecular mechanisms of vertebrate lens development

    PubMed Central

    Cvekl, Aleš; Ashery-Padan, Ruth

    2014-01-01

    The ocular lens is a model system for understanding important aspects of embryonic development, such as cell specification and the spatiotemporally controlled formation of a three-dimensional structure. The lens, which is characterized by transparency, refraction and elasticity, is composed of a bulk mass of fiber cells attached to a sheet of lens epithelium. Although lens induction has been studied for over 100 years, recent findings have revealed a myriad of extracellular signaling pathways and gene regulatory networks, integrated and executed by the transcription factor Pax6, that are required for lens formation in vertebrates. This Review summarizes recent progress in the field, emphasizing the interplay between the diverse regulatory mechanisms employed to form lens progenitor and precursor cells and highlighting novel opportunities to fill gaps in our understanding of lens tissue morphogenesis. PMID:25406393

  2. Hox genes and regional patterning of the vertebrate body plan.

    PubMed

    Mallo, Moises; Wellik, Deneen M; Deschamps, Jacqueline

    2010-08-01

    Several decades have passed since the discovery of Hox genes in the fruit fly Drosophila melanogaster. Their unique ability to regulate morphologies along the anteroposterior (AP) axis (Lewis, 1978) earned them well-deserved attention as important regulators of embryonic development. Phenotypes due to loss- and gain-of-function mutations in mouse Hox genes have revealed that the spatio-temporally controlled expression of these genes is critical for the correct morphogenesis of embryonic axial structures. Here, we review recent novel insight into the modalities of Hox protein function in imparting specific identity to anatomical regions of the vertebral column, and in controlling the emergence of these tissues concomitantly with providing them with axial identity. The control of these functions must have been intimately linked to the shaping of the body plan during evolution.

  3. Soluble factors from the notochordal-rich intervertebral disc inhibit endothelial cell invasion and vessel formation in the presence and absence of pro-inflammatory cytokines

    PubMed Central

    Cornejo, M.C.; Cho, S.K.; Giannarelli, C.; Iatridis, J.C.; Purmessur, D.

    2015-01-01

    Background Chronic low back pain can be associated with the pathological ingrowth of blood vessels and nerves into intervertebral discs (IVDs). The notochord patterns the IVD during development and is a source of anti-angiogenic soluble factors such as Noggin and Chondroitin sulfate (CS). These factors may form the basis for a new minimally invasive strategy to target angiogenesis in the IVD. Objective To examine the anti-angiogenic potential of soluble factors from notochordal cells (NCs) and candidates Noggin and CS under healthy culture conditions and in the presence of pro-inflammatory mediators. Design NC conditioned media (NCCM) was generated from porcine NC-rich nucleus pulposus tissue. To assess the effects of NCCM, CS and Noggin on angiogenesis, cell invasion and tubular formation assays were performed using human umbilical vein endothelial cells (HUVECs) ± tumor necrosis factor alpha (TNFα [10 ng/ml]). vascular endothelial growth factor (VEGF)-A, MMP-7, interleukin-6 (IL-6) and IL-8 mRNA levels were assessed using qRT-PCR. Results NCCM (10 & 100%), CS (10 and 100 μg) and Noggin (10 and 100 ng) significantly decreased cell invasion of HUVECs with and without TNFα. NCCM 10% and Noggin 10 ng inhibited tubular formation with and without TNFα and CS 100 μg inhibited tubules in Basal conditions whereas CS 10 μg inhibited tubules with TNFα. NCCM significantly decreased VEGF-A, MMP-7 and IL-6 mRNA levels in HUVECs with and without TNFα. CS and Noggin had no effects on gene expression. Conclusions We provide the first evidence that soluble factors from NCs can inhibit angiogenesis by suppressing VEGF signaling. Notochordal-derived ligands are a promising minimally invasive strategy targeting neurovascular ingrowth and pain in the degenerated IVD. PMID:25534363

  4. Vertebral function during tadpole locomotion.

    PubMed

    Azizi, Emanuel; Landberg, Tobias; Wassersug, Richard J

    2007-01-01

    Most anuran larvae show large lateral oscillations at both the tip of the tail and the snout while swimming in a straight line. Although the lateral deflections at the snout have long been considered an inefficient aspect of tadpole locomotion, a recent hydrodynamic model suggests that they may in fact help generate thrust. It is not clear though exactly where this bending takes place. The vertebral column is extremely short and seemingly inflexible in anurans, and any axial flexion that might occur there is hidden within the globose body of the tadpole. Here we test the hypothesis that lateral deflections of the snout correlate with bending of the vertebral column within the torso of tadpoles. To quantify vertebral curvature, three sonomicrometry crystals were surgically implanted along the dorsal midline in locations corresponding to the anterior, middle, and posterior region of the presacral vertebral column. Swimming trials were conducted in a flume where synchronized video recordings were collected in dorsal view. Our results confirm that cyclic lateral bending occurs along the vertebral column during swimming and indicate that vertebral curvature is temporally in phase with lateral oscillation of the snout. Lateral oscillation of the snout increased significantly with increasing vertebral curvature. Similarly, tail beat amplitude also increases significantly with increasing vertebral curvature. Our results suggest that cyclic lateral flexion of the vertebral column, activated by the axial muscle within the torso of tadpoles contributes to snout oscillations and the generation of thrust during undulatory swimming in anuran larvae.

  5. Adhesive and Signaling Functions of Cadherins and Catenins in Vertebrate Development

    PubMed Central

    Stepniak, Ewa; Radice, Glenn L.; Vasioukhin, Valeri

    2009-01-01

    Properly regulated intercellular adhesion is critical for normal development of all metazoan organisms. Adherens junctions play an especially prominent role in development because they link the adhesive function of cadherin–catenin protein complexes to the dynamic forces of the actin cytoskeleton, which helps to orchestrate a spatially confined and very dynamic assembly of intercellular connections. Intriguingly, in addition to maintaining intercellular adhesion, cadherin–catenin proteins are linked to several major developmental signaling pathways crucial for normal morphogenesis. In this article we will highlight the key genetic studies that uncovered the role of cadherin–catenin proteins in vertebrate development and discuss the potential role of these proteins as molecular biosensors of external cellular microenvironment that may spatially confine signaling molecules and polarity cues to orchestrate cellular behavior throughout the complex process of normal morphogenesis. PMID:20066120

  6. The ‘Tully monster’ is a vertebrate

    NASA Astrophysics Data System (ADS)

    McCoy, Victoria E.; Saupe, Erin E.; Lamsdell, James C.; Tarhan, Lidya G.; McMahon, Sean; Lidgard, Scott; Mayer, Paul; Whalen, Christopher D.; Soriano, Carmen; Finney, Lydia; Vogt, Stefan; Clark, Elizabeth G.; Anderson, Ross P.; Petermann, Holger; Locatelli, Emma R.; Briggs, Derek E. G.

    2016-04-01

    Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the ‘problem of the problematica’, particularly the ‘weird wonders’ of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium, popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans, polychaetes, gastropods, conodonts, and the stem arthropod Opabinia. Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes. We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys, a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years.

  7. Vertebral fracture classification

    NASA Astrophysics Data System (ADS)

    de Bruijne, Marleen; Pettersen, Paola C.; Tankó, László B.; Nielsen, Mads

    2007-03-01

    A novel method for classification and quantification of vertebral fractures from X-ray images is presented. Using pairwise conditional shape models trained on a set of healthy spines, the most likely unfractured shape is estimated for each of the vertebrae in the image. The difference between the true shape and the reconstructed normal shape is an indicator for the shape abnormality. A statistical classification scheme with the two shapes as features is applied to detect, classify, and grade various types of deformities. In contrast with the current (semi-)quantitative grading strategies this method takes the full shape into account, it uses a patient-specific reference by combining population-based information on biological variation in vertebra shape and vertebra interrelations, and it provides a continuous measure of deformity. Good agreement with manual classification and grading is demonstrated on 204 lateral spine radiographs with in total 89 fractures.

  8. HANGING ON FOR THE RIDE: ADHESION TO THE EXTRACELLULAR MATRIX MEDIATES CELLULAR RESPONSES IN SKELETAL MUSCLE MORPHOGENESIS AND DISEASE

    PubMed Central

    Goody, Michelle F.; Sher, Roger B.; Henry, Clarissa A.

    2015-01-01

    Skeletal muscle specification and morphogenesis during early development are critical for normal physiology. In addition to mediating locomotion, skeletal muscle is a secretory organ that contributes to metabolic homeostasis. Muscle is a highly adaptable tissue, as evidenced by the ability to increase muscle cell size and/or number in response to weight bearing exercise. Conversely, muscle wasting can occur during aging (sarcopenia), cancer (cancer cachexia), extended hospital stays (disuse atrophy), and in many genetic diseases collectively known as the muscular dystrophies and myopathies. It is therefore of great interest to understand the cellular and molecular mechanisms that mediate skeletal muscle development and adaptation. Muscle morphogenesis transforms short muscle precursor cells into long, multinucleate myotubes that anchor to tendons via the myotendinous junction. This process requires carefully orchestrated interactions between cells and their extracellular matrix microenvironment. These interactions are dynamic, allowing muscle cells to sense biophysical, structural, organizational, and/or signaling changes within their microenvironment and respond appropriately. In many musculoskeletal diseases, these cell adhesion interactions are disrupted to such a degree that normal cellular adaptive responses are not sufficient to compensate for accumulating damage. Thus, one major focus of current research is to identify the cell adhesion mechanisms that drive muscle morphogenesis, with the hope that understanding how muscle cell adhesion promotes the intrinsic adaptability of muscle tissue during development may provide insight into potential therapeutic approaches for muscle diseases. Our objectives in this review are to highlight recent studies suggesting conserved roles for cell-extracellular matrix adhesion in vertebrate muscle morphogenesis and cellular adaptive responses in animal models of muscle diseases. PMID:25592225

  9. Comparative studies on limb morphogenesis in mice and bats: a functional genetic approach towards a molecular understanding of diversity in organ formation.

    PubMed

    Cretekos, C J; Rasweiler, J J; Behringer, R R

    2001-01-01

    The basis of species-specific morphogenesis has been a topic of fascination and speculation for centuries. In 1828, Karl Ernst von Baer noted that at the pharyngula stage of development all vertebrate embryos are morphologically very similar. Most subsequent hypotheses have proposed that the vertebrate body plan develops by a conserved mechanism, and that divergent forms develop by differential elaboration on this basic plan. Gene cloning and expression studies have largely confirmed that the genetic pathways of embryonic patterning are highly conserved. The finding that the proteins encoded by paralogous and orthologous genes within and between species can functionally replace each another is no longer novel; in most cases this is the expected result. How, then, does divergent morphology arise between species? One hypothesis that fits well with comparative data is that divergent morphogenesis arises from genetic differences in the timing, level and pattern of orthologous gene expression during development. This idea is being tested using a functional genetic approach comparing limb morphogenesis between the mouse and bat. PMID:11999322

  10. Comparative studies on limb morphogenesis in mice and bats: a functional genetic approach towards a molecular understanding of diversity in organ formation.

    PubMed

    Cretekos, C J; Rasweiler, J J; Behringer, R R

    2001-01-01

    The basis of species-specific morphogenesis has been a topic of fascination and speculation for centuries. In 1828, Karl Ernst von Baer noted that at the pharyngula stage of development all vertebrate embryos are morphologically very similar. Most subsequent hypotheses have proposed that the vertebrate body plan develops by a conserved mechanism, and that divergent forms develop by differential elaboration on this basic plan. Gene cloning and expression studies have largely confirmed that the genetic pathways of embryonic patterning are highly conserved. The finding that the proteins encoded by paralogous and orthologous genes within and between species can functionally replace each another is no longer novel; in most cases this is the expected result. How, then, does divergent morphology arise between species? One hypothesis that fits well with comparative data is that divergent morphogenesis arises from genetic differences in the timing, level and pattern of orthologous gene expression during development. This idea is being tested using a functional genetic approach comparing limb morphogenesis between the mouse and bat.

  11. Morphogenesis in Belousov-Zhabotinsky microdroplets

    NASA Astrophysics Data System (ADS)

    Li, Ning; Tompkins, Nathan; Girabawe, Camille; Epstein, Irving; Fraden, Seth; Brandeis/Mrsec Team

    2013-03-01

    We present experimental evidence for the six cases Alan Turing predicted using linear stability analysis in his 1952 paper ``The chemical basis of morphogenesis'' in our reaction diffusion system. Our experimental system consists of a microfluidically generated microemulsion consisting of Ru(bipy)3 catalyzed light sensitive BZ aqueous droplets which are diffusively coupled through oil gaps. We observed that some droplets grow and others shrink due to the unequal consumption of chemicals in the droplets which leads to an osmotic pressure change, as Turing predicted in his paper. The initial and boundary conditions of our system were controlled by programmable illumination via the light sensitive catalyst Ru(bipy)3. Simulation and linear stability analysis were performed and compared with the experiments. Funded by MRSEC.

  12. Morphogenesis of the human excretory lacrimal system

    PubMed Central

    de la Cuadra-Blanco, C; Peces-Peña, M D; Jáñez-Escalada, L; Mérida-Velasco, J R

    2006-01-01

    The aim of this study was to determine the principal developmental stages in the formation of the excretory lacrimal system in humans and to establish its morphogenetic period. The study was performed using light microscopy on serial sections of 51 human specimens: 33 embryos and 18 fetuses ranging from 8 to 137 mm crown–rump length (CR; 5–16 weeks of development). Three stages were identified in the morphogenesis of the excretory lacrimal system: (1) the formative stage of the lacrimal lamina (Carnegie stages 16–18); (2) the formative stage of the lacrimal cord (Carnegie stages 19–23); and (3) the maturative stage of the excretory lacrimal system, from the 9th week of development onward. A three-dimensional reconstruction of the excretory lacrimal system was performed from serial sections of an embryo at the end of the embryonic period (27 mm CR). PMID:16879594

  13. Physical forces regulate plant development and morphogenesis

    PubMed Central

    Sampathkumar, Arun; Yan, An; Krupinski, Pawel; Meyerowitz, Elliot M.

    2014-01-01

    Plant cells in tissues experience mechanical stress not only as a result of high turgor, but also through interaction with their neighbors. Cells can expand at different rates and in different directions from neighbors with which they share a cell wall. This in connection with specific tissue shapes and properties of the cell wall material can lead to intricate stress patterns throughout the tissue. Two cellular responses to mechanical stress are a microtubule cytoskeletal response that directs new wall synthesis so as to resist stress, and a hormone transporter response that regulates transport of the hormone auxin, a regulator of cell expansion. Shape changes in plant tissues affect the pattern of stresses in the tissues, and at the same time, via the cellular stress responses, the pattern of stresses controls cell growth, which in turn changes tissue shape, and stress pattern. This feedback loop controls plant morphogenesis, and explains several previously mysterious aspects of plant growth. PMID:24845680

  14. Physical forces regulate plant development and morphogenesis.

    PubMed

    Sampathkumar, Arun; Yan, An; Krupinski, Pawel; Meyerowitz, Elliot M

    2014-05-19

    Plant cells in tissues experience mechanical stress not only as a result of high turgor, but also through interaction with their neighbors. Cells can expand at different rates and in different directions from neighbors with which they share a cell wall. This in connection with specific tissue shapes and properties of the cell wall material can lead to intricate stress patterns throughout the tissue. Two cellular responses to mechanical stress are a microtubule cytoskeletal response that directs new wall synthesis so as to resist stress, and a hormone transporter response that regulates transport of the hormone auxin, a regulator of cell expansion. Shape changes in plant tissues affect the pattern of stresses in the tissues, and at the same time, via the cellular stress responses, the pattern of stresses controls cell growth, which in turn changes tissue shape, and stress pattern. This feedback loop controls plant morphogenesis, and explains several previously mysterious aspects of plant growth. PMID:24845680

  15. Morphogenesis of the human excretory lacrimal system.

    PubMed

    de la Cuadra-Blanco, C; Peces-Peña, M D; Jáñez-Escalada, L; Mérida-Velasco, J R

    2006-08-01

    The aim of this study was to determine the principal developmental stages in the formation of the excretory lacrimal system in humans and to establish its morphogenetic period. The study was performed using light microscopy on serial sections of 51 human specimens: 33 embryos and 18 fetuses ranging from 8 to 137 mm crown-rump length (CR; 5-16 weeks of development). Three stages were identified in the morphogenesis of the excretory lacrimal system: (1) the formative stage of the lacrimal lamina (Carnegie stages 16-18); (2) the formative stage of the lacrimal cord (Carnegie stages 19-23); and (3) the maturative stage of the excretory lacrimal system, from the 9th week of development onward. A three-dimensional reconstruction of the excretory lacrimal system was performed from serial sections of an embryo at the end of the embryonic period (27 mm CR).

  16. Micropatterning of cells reveals chiral morphogenesis

    PubMed Central

    2013-01-01

    Invariant left-right (LR) patterning or chirality is critical for embryonic development. The loss or reversal of LR asymmetry is often associated with malformations and disease. Although several theories have been proposed, the exact mechanism of the initiation of the LR symmetry has not yet been fully elucidated. Recently, chirality has been detected within single cells as well as multicellular structures using several in vitro approaches. These studies demonstrated the universality of cell chirality, its dependence on cell phenotype, and the role of physical boundaries. In this review, we discuss the theories for developmental LR asymmetry, compare various in vitro cell chirality model systems, and highlight possible roles of cell chirality in stem cell differentiation. We emphasize that the in vitro cell chirality systems have great promise for helping unveil the nature of chiral morphogenesis in development. PMID:23672821

  17. Opportunistic Identification of Vertebral Fractures.

    PubMed

    Adams, Judith E

    2016-01-01

    Vertebral fractures are powerful predictors of future fracture, so, their identification is important to ensure that patients are commenced on appropriate bone protective or bone-enhancing therapy. Risk factors (e.g., low bone mineral density and increasing age) and symptoms (back pain, loss of height) may herald the presence of vertebral fractures, which are usually confirmed by performing spinal radiographs or, increasingly, using vertebral fracture assessment with dual-energy X-ray absorptiometry scanners. However, a large number (30% or more) of vertebral fractures are asymptomatic and do not come to clinical attention. There is, therefore, scope for opportunistic (fortuitous) identification of vertebral fractures from various imaging modalities (radiographs, computed tomography, magnetic resonance imaging, and radionuclide scans) performed for other clinical indications and which include the spine in the field of view, with midline sagittal reformatted images from computed tomography having the greatest potential for such opportunistic detection. Numerous studies confirm this potential for identification but consistently find underreporting of vertebral fractures. So, a valuable opportunity to improve the management of patients at increased risk of future fracture is being squandered. Educational training programs for all clinicians and constant reiteration, stressing the importance of the accurate and clear reporting of vertebral fractures ("you only see what you look for"), can improve the situation, and automated computer-aided diagnostic tools also show promise to solve the problem of this underreporting of vertebral fractures.

  18. Opportunistic Identification of Vertebral Fractures.

    PubMed

    Adams, Judith E

    2016-01-01

    Vertebral fractures are powerful predictors of future fracture, so, their identification is important to ensure that patients are commenced on appropriate bone protective or bone-enhancing therapy. Risk factors (e.g., low bone mineral density and increasing age) and symptoms (back pain, loss of height) may herald the presence of vertebral fractures, which are usually confirmed by performing spinal radiographs or, increasingly, using vertebral fracture assessment with dual-energy X-ray absorptiometry scanners. However, a large number (30% or more) of vertebral fractures are asymptomatic and do not come to clinical attention. There is, therefore, scope for opportunistic (fortuitous) identification of vertebral fractures from various imaging modalities (radiographs, computed tomography, magnetic resonance imaging, and radionuclide scans) performed for other clinical indications and which include the spine in the field of view, with midline sagittal reformatted images from computed tomography having the greatest potential for such opportunistic detection. Numerous studies confirm this potential for identification but consistently find underreporting of vertebral fractures. So, a valuable opportunity to improve the management of patients at increased risk of future fracture is being squandered. Educational training programs for all clinicians and constant reiteration, stressing the importance of the accurate and clear reporting of vertebral fractures ("you only see what you look for"), can improve the situation, and automated computer-aided diagnostic tools also show promise to solve the problem of this underreporting of vertebral fractures. PMID:26412139

  19. Chemical ecology of vertebrate carrion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vertebrate carrion is a nutrient-rich, ephemeral resource that is utilized by many different organisms ranging from vertebrate and invertebrate scavengers to microbes. The organisms that consume carrion play an important ecological role, as decomposition is vital to ecosystem function. Without the...

  20. Palate Morphogenesis: Current Understanding and Future Directions

    PubMed Central

    Greene, Robert M.; Pisano, M. Michele

    2011-01-01

    In the past, most scientists conducted their inquiries of nature via inductivism, the patient accumulation of “pieces of information” in the pious hope that the sum of the parts would clarify the whole. Increasingly, modern biology employs the tools of bioinformatics and systems biology in attempts to reveal the “big picture.” Most successful laboratories engaged in the pursuit of the secrets of embryonic development, particularly those whose research focus is craniofacial development, pursue a middle road where research efforts embrace, rather than abandon, what some have called the “pedestrian” qualities of inductivism, while increasingly employing modern data mining technologies. The secondary palate has provided an excellent paradigm that has enabled examination of a wide variety of developmental processes. Examination of cellular signal transduction, as it directs embryogenesis, has proven exceptionally revealing with regard to clarification of the “facts” of palatal ontogeny—at least the facts as we currently understand them. Herein, we review the most basic fundamentals of orofacial embryology and discuss how functioning of TGFβ, BMP, Shh, and Wnt signal transduction pathways contributes to palatal morphogenesis. Our current understanding of palate medial edge epithelial differentiation is also examined. We conclude with a discussion of how the rapidly expanding field of epigenetics, particularly regulation of gene expression by miRNAs and DNA methylation, is critical to control of cell and tissue differentiation, and how examination of these epigenetic processes has already begun to provide a better understanding of, and greater appreciation for, the complexities of palatal morphogenesis. PMID:20544696

  1. Comparative anatomy: all vertebrates do have vertebrae.

    PubMed

    Janvier, Philippe

    2011-09-13

    In contrast to lampreys and jawed vertebrates, hagfishes were thought to lack vertebrae. Now, long overlooked vertebral rudiments have been analysed in hagfish, suggesting that vertebrae existed in the last common ancestor of all vertebrates.

  2. parachute/n-cadherin is required for morphogenesis and maintained integrity of the zebrafish neural tube.

    PubMed

    Lele, Zsolt; Folchert, Anja; Concha, Miguel; Rauch, Gerd-Jörg; Geisler, Robert; Rosa, Frédéric; Wilson, Steve W; Hammerschmidt, Matthias; Bally-Cuif, Laure

    2002-07-01

    N-cadherin (Ncad) is a classical cadherin that is implicated in several aspects of vertebrate embryonic development, including somitogenesis, heart morphogenesis, neural tube formation and establishment of left-right asymmetry. However, genetic in vivo analyses of its role during neural development have been rather limited. We report the isolation and characterization of the zebrafish parachute (pac) mutations. By mapping and candidate gene analysis, we demonstrate that pac corresponds to a zebrafish n-cadherin (ncad) homolog. Three mutant alleles were sequenced and each is likely to encode a non-functional Ncad protein. All result in a similar neural tube phenotype that is most prominent in the midbrain, hindbrain and the posterior spinal cord. Neuroectodermal cell adhesion is altered, and convergent cell movements during neurulation are severely compromised. In addition, many neurons become progressively displaced along the dorsoventral and the anteroposterior axes. At the cellular level, loss of Ncad affects beta-catenin stabilization/localization and causes mispositioned and increased mitoses in the dorsal midbrain and hindbrain, a phenotype later correlated with enhanced apoptosis and the appearance of ectopic neurons in these areas. Our results thus highlight novel and crucial in vivo roles for Ncad in the control of cell convergence, maintenance of neuronal positioning and dorsal cell proliferation during vertebrate neural tube development.

  3. The small GTPase Rac1 regulates auditory hair cell morphogenesis

    PubMed Central

    Grimsley-Myers, Cynthia M.; Sipe, Conor W.; Géléoc, Gwenaëllle S.G.; Lu, Xiaowei

    2010-01-01

    Morphogenesis of sensory hair cells, in particular their mechanotransduction organelle, the stereociliary bundle, requires highly organized remodeling of the actin cytoskeleton. The roles of Rho family small GTPases during this process remain unknown. Here we show that deletion of Rac1 in the otic epithelium resulted in severe defects in cochlear epithelial morphogenesis. The mutant cochlea was severely shortened with a reduced number of auditory hair cells and cellular organization of the auditory sensory epithelium was abnormal. Rac1 mutant hair cells also displayed defects in planar cell polarity and morphogenesis of the stereociliary bundle, including bundle fragmentation or deformation, and mispositioning or absence of the kinocilium. We further demonstrate that a Rac-PAK signaling pathway mediates kinocilium-stereocilia interactions and is required for cohesion of the stereociliary bundle. Together, these results reveal a critical function of Rac1 in morphogenesis of the auditory sensory epithelium and stereociliary bundle. PMID:20016102

  4. Evolutionary Origins of C-Terminal (GPP)n 3-Hydroxyproline Formation in Vertebrate Tendon Collagen

    PubMed Central

    Hudson, David M.; Werther, Rachel; Weis, MaryAnn; Wu, Jiann-Jiu; Eyre, David R.

    2014-01-01

    Approximately half the proline residues in fibrillar collagen are hydroxylated. The predominant form is 4-hydroxyproline, which helps fold and stabilize the triple helix. A minor form, 3-hydroxyproline, still has no clear function. Using peptide mass spectrometry, we recently revealed several previously unknown molecular sites of 3-hydroxyproline in fibrillar collagen chains. In fibril-forming A-clade collagen chains, four new partially occupied 3-hydroxyproline sites were found (A2, A3, A4 and (GPP)n) in addition to the fully occupied A1 site at Pro986. The C-terminal (GPP)n motif has five consecutive GPP triplets in α1(I), four in α2(I) and three in α1(II), all subject to 3-hydroxylation. The evolutionary origins of this substrate sequence were investigated by surveying the pattern of its 3-hydroxyproline occupancy from early chordates through amphibians, birds and mammals. Different tissue sources of type I collagen (tendon, bone and skin) and type II collagen (cartilage and notochord) were examined by mass spectrometry. The (GPP)n domain was found to be a major substrate for 3-hydroxylation only in vertebrate fibrillar collagens. In higher vertebrates (mouse, bovine and human), up to five 3-hydroxyproline residues per (GPP)n motif were found in α1(I) and four in α2(I), with an average of two residues per chain. In vertebrate type I collagen the modification exhibited clear tissue specificity, with 3-hydroxyproline prominent only in tendon. The occupancy also showed developmental changes in Achilles tendon, with increasing 3-hydroxyproline levels with age. The biological significance is unclear but the level of 3-hydroxylation at the (GPP)n site appears to have increased as tendons evolved and shows both tendon type and developmental variations within a species. PMID:24695516

  5. The human vertebral column at the end of the embryonic period proper. 2. The occipitocervical region.

    PubMed Central

    O'Rahilly, R; Müller, F; Meyer, D B

    1983-01-01

    The present investigation of the cervical region of the vertebral column at eight post-ovulatory weeks is the first such study based on precise reconstructions of staged embryos. At the end of the embryonic period proper, a typical vertebra is a U-shaped piece of cartilage characterized by spina bifida occulta. The notochord ascends through the centra and leaves the dens to enter the basal plate of the skull. The median column of the axis comprises three parts (designated X, Y, Z) which persist well into the fetal period. They are related to the first, second and third cervical nerves, respectively. Part X may project into the foramen magnum and form an occipito-axial joint. Part Z appears to be the centrum of the axis. The articular columns of the cervical vertebrae are twofold, as in the adult: an anterior (atlanto-occipital and atlanto-axial) and a posterior (from the lower aspect of the axis downwards). Alar and transverse ligaments are present. Cavitation is not found in the embryonic period in either the atlanto-occipital or zygapophysial joints, and is generally not present in the median atlanto-axial joint either. Most of the transverse processes exhibit anterior and posterior tubercles. An 'intertubercular lamella' may or may not be present, i.e. the foramina transversaria are being formed around the vertebral artery. The spinal ganglia are generally partly in the vertebral canal and partly on the neural arches, medial to the articular processes. During the fetal period, the articular processes shift to a coronal position and this alteration appears to be associated with a corresponding change in the location of the spinal ganglia. Images Fig. 4 Fig. 7 PMID:6833119

  6. Roles for FGF in lamprey pharyngeal pouch formation and skeletogenesis highlight ancestral functions in the vertebrate head.

    PubMed

    Jandzik, David; Hawkins, M Brent; Cattell, Maria V; Cerny, Robert; Square, Tyler A; Medeiros, Daniel M

    2014-02-01

    A defining feature of vertebrates (craniates) is a pronounced head supported and protected by a cellularized endoskeleton. In jawed vertebrates (gnathostomes), the head skeleton is made of rigid three-dimensional elements connected by joints. By contrast, the head skeleton of modern jawless vertebrates (agnathans) consists of thin rods of flexible cellular cartilage, a condition thought to reflect the ancestral vertebrate state. To better understand the origin and evolution of the gnathostome head skeleton, we have been analyzing head skeleton development in the agnathan, lamprey. The fibroblast growth factors FGF3 and FGF8 have various roles during head development in jawed vertebrates, including pharyngeal pouch morphogenesis, patterning of the oral skeleton and chondrogenesis. We isolated lamprey homologs of FGF3, FGF8 and FGF receptors and asked whether these functions are ancestral features of vertebrate development or gnathostome novelties. Using gene expression and pharmacological agents, we found that proper formation of the lamprey head skeleton requires two phases of FGF signaling: an early phase during which FGFs drive pharyngeal pouch formation, and a later phase when they directly regulate skeletal differentiation and patterning. In the context of gene expression and functional studies in gnathostomes, our results suggest that these roles for FGFs arose in the first vertebrates and that the evolution of the jaw and gnathostome cellular cartilage was driven by changes developmentally downstream from pharyngeal FGF signaling.

  7. The Arabidopsis embryo as a miniature morphogenesis model.

    PubMed

    Wendrich, Jos R; Weijers, Dolf

    2013-07-01

    Four basic ingredients of morphogenesis, oriented cell division and expansion, cell-cell communication and cell fate specification allow plant cells to develop into a wide variety of organismal architectures. A central question in plant biology is how these cellular processes are regulated and orchestrated. Here, we present the advantages of the early Arabidopsis embryo as a model for studying the control of morphogenesis. All ingredients of morphogenesis converge during embryogenesis, and the highly predictable nature of embryo development offers unprecedented opportunities for understanding their regulation in time and space. In this review we describe the morphogenetic principles underlying embryo patterning and discuss recent advances in their regulation. Morphogenesis is under tight transcriptional control and most genes that were identified as important regulators of embryo patterning encode transcription factors or components of signaling pathways. There exists, therefore, a large gap between the transcriptional control of embryo morphogenesis and the cellular execution. We describe the first such connections, and propose future directions that should help bridge this gap and generate comprehensive understanding of the control of morphogenesis.

  8. A conceptual model of morphogenesis and regeneration

    PubMed Central

    Tosenberger, A.; Bessonov, N.; Levin, M.; Reinberg, N.; Volpert, V.; Morozova, N.

    2016-01-01

    This paper is devoted to computer modelling of the development and regeneration of multicellular biological structures. Some species (e.g., planaria and salamanders) are able to regenerate parts of their body after amputation damage, but the global rules governing cooperative cell behaviour during morphogenesis are not known. Here, we consider a simplified model organism, which consists of tissues formed around special cells that can be interpreted as stem cells. We assume that stem cells communicate with each other by a set of signals, and that the values of these signals depend on the distance between cells. Thus the signal distribution characterizes location of stem cells. If the signal distribution is changed, then the difference between the initial and the current signal distribution affects the behaviour of stem cells – e.g. as a result of an amputation of a part of tissue the signal distribution changes which stimulates stem cells to migrate to new locations, appropriate for regeneration of the proper pattern. Moreover, as stem cells divide and form tissues around them, they control the form and the size of regenerating tissues. This two-level organization of the model organism, with global regulation of stem cells and local regulation of tissues, allows its reproducible development and regeneration. PMID:25822060

  9. Mechanical feedback stabilizes budding yeast morphogenesis

    NASA Astrophysics Data System (ADS)

    Banavar, Samhita; Trogdon, Michael; Petzold, Linda; Campas, Otger

    Walled cells have the ability to remodel their shape while sustaining an internal turgor pressure that can reach values up to 10 atmospheres. This requires a tight and simultaneous regulation of cell wall assembly and mechanochemistry, but the underlying mechanisms by which this is achieved remain unclear. Using the growth of mating projections in budding yeast (S. cerevisiae) as a motivating example, we have developed a theoretical description that couples the mechanics of cell wall expansion and assembly via a mechanical feedback. In the absence of a mechanical feedback, cell morphogenesis is inherently unstable. The presence of a mechanical feedback stabilizes changes in cell shape and growth, and provides a mechanism to prevent cell lysis in a wide range of conditions. We solve for the dynamics of the system and obtain the different dynamical regimes. In particular, we show that several parameters affect the stability of growth, including the strength of mechanical feedback in the system. Finally, we compare our results to existing experimental data.

  10. Epithelial fusion during neural tube morphogenesis

    PubMed Central

    Pai, Yun-Jin; Abdullah, N.L.; Mohd.-Zin, S.W.; Mohammed, R. S.; Rolo, Ana; Greene, Nicholas D.E.; Abdul-Aziz, Noraishah M.; Copp, Andrew J.

    2013-01-01

    Adhesion and fusion of epithelial sheets marks the completion of many morphogenetic events during embryogenesis. Neural tube closure involves an epithelial fusion sequence in which the apposing neural folds adhere initially via cellular protrusions, proceed to a more stable union, and subsequently undergo remodelling of the epithelial structures to yield a separate neural tube roof plate and overlying non-neural ectoderm. Cellular protrusions comprise lamellipodia and filopodia, and studies in several different systems emphasise the critical role of RhoGTPases in their regulation. How epithelia establish initial adhesion is poorly understood but, in neurulation, may involve interactions between EphA receptors and their ephrinA ligands. Epithelial remodelling is spatially and temporally correlated with apoptosis in the dorsal neural tube midline, but experimental inhibition of this cell death does not prevent fusion and remodelling. A variety of molecular signalling systems have been implicated in the late events of morphogenesis, but genetic redundancy, for example among the integrins and laminins, makes identification of the critical players challenging. An improved understanding of epithelial fusion can provide insights into normal developmental processes, and may also indicate the mode of origin of clinically important birth defects. PMID:22945349

  11. Multiscale information modelling for heart morphogenesis

    NASA Astrophysics Data System (ADS)

    Abdulla, T.; Imms, R.; Schleich, J. M.; Summers, R.

    2010-07-01

    Science is made feasible by the adoption of common systems of units. As research has become more data intensive, especially in the biomedical domain, it requires the adoption of a common system of information models, to make explicit the relationship between one set of data and another, regardless of format. This is being realised through the OBO Foundry to develop a suite of reference ontologies, and NCBO Bioportal to provide services to integrate biomedical resources and functionality to visualise and create mappings between ontology terms. Biomedical experts tend to be focused at one level of spatial scale, be it biochemistry, cell biology, or anatomy. Likewise, the ontologies they use tend to be focused at a particular level of scale. There is increasing interest in a multiscale systems approach, which attempts to integrate between different levels of scale to gain understanding of emergent effects. This is a return to physiological medicine with a computational emphasis, exemplified by the worldwide Physiome initiative, and the European Union funded Network of Excellence in the Virtual Physiological Human. However, little work has been done on how information modelling itself may be tailored to a multiscale systems approach. We demonstrate how this can be done for the complex process of heart morphogenesis, which requires multiscale understanding in both time and spatial domains. Such an effort enables the integration of multiscale metrology.

  12. [The flagellum: from cell motility to morphogenesis].

    PubMed

    Kohl, Linda; Robinson, Derrick; Bastin, Philippe

    2003-01-01

    Flagella and cilia are elaborate cytoskeletal structures conserved from protists to mammals, where they fulfil functions related to motility or sensitivity. We demonstrate a novel role for the flagellum in the control of cell morphogenesis and division of Trypanosoma brucei. To investigate flagellum functions, its formation was perturbed by inducible RNA interference silencing of components required for intraflagellar transport (IFT), a dynamic process necessary for flagellum assembly. First, we show that down-regulation of IFT leads to assembly of a shorter flagellum. Strikingly, cells with a shorter flagellum are smaller, with a direct correlation between flagellum length and cell size. Detailed morphogenetic analysis reveals that the tip of the new flagellum defines the point where cytokinesis is initiated. Furthermore, when new flagellum formation is completely blocked, non-flagellated cells are very short, lose their normal shape and polarity and fail to undergo cytokinesis. We show that flagellum elongation controls formation of cytoskeletal structures present in the cell body that act as molecular organisers of the cell.

  13. Local mechanisms in sex specific morphogenesis.

    PubMed

    Drews, U

    2000-01-01

    Sex determination in mammals occurs on three levels. Segregation of sex chromosomes determines the chromosomal sex. Sry on the Y chromosome induces formation of a testis which in turn regulates via AMH and testosterone the development of the genital tract and the external phenotype. Recently a number of new factors have been described, which affect sexual development but have not yet found a place in the above canonical scheme of sex determination. For the purpose of this review, the factors are aligned according to their quality as transcription factors, steroid hormones, or growth factors. In this web of regulatory factors, the classical sex determining factors have evolved as master mechanisms while others function as slaves, or were totally suppressed. In this context, androgens acquired a dominant role in mammalian development. Androgens determine the morphogenesis of the genital tract. The effects of androgens are mediated by local cellular interactions. In the cranial section of the Wolffian duct the androgen receptor appears in the epithelium and mediates maintenance of the duct via an epithelial factor. In the caudal section of the duct the androgen receptor is expressed in the embryonic mesenchyme. Vesicular glands are induced via a morphogenetically active mesenchymal condensation, while the epithelial buds are primarily AR androgen receptor negative. The dominant role of androgens and formation of a vagina evolved together at the transition to eutherian mammals. Under this aspect, the role of androgens in the development of the vagina is analyzed.

  14. Lymphatic regulation in nonmammalian vertebrates.

    PubMed

    Hedrick, Michael S; Hillman, Stanley S; Drewes, Robert C; Withers, Philip C

    2013-08-01

    All vertebrate animals share in common the production of lymph through net capillary filtration from their closed circulatory system into their tissues. The balance of forces responsible for net capillary filtration and lymph formation is described by the Starling equation, but additional factors such as vascular and interstitial compliance, which vary markedly among vertebrates, also have a significant impact on rates of lymph formation. Why vertebrates show extreme variability in rates of lymph formation and how nonmammalian vertebrates maintain plasma volume homeostasis is unclear. This gap hampers our understanding of the evolution of the lymphatic system and its interaction with the cardiovascular system. The evolutionary origin of the vertebrate lymphatic system is not clear, but recent advances suggest common developmental factors for lymphangiogenesis in teleost fishes, amphibians, and mammals with some significant changes in the water-land transition. The lymphatic system of anuran amphibians is characterized by large lymphatic sacs and two pairs of lymph hearts that return lymph into the venous circulation but no lymph vessels per se. The lymphatic systems of reptiles and some birds have lymph hearts, and both groups have extensive lymph vessels, but their functional role in both lymph movement and plasma volume homeostasis is almost completely unknown. The purpose of this review is to present an evolutionary perspective in how different vertebrates have solved the common problem of the inevitable formation of lymph from their closed circulatory systems and to point out the many gaps in our knowledge of this evolutionary progression.

  15. Lymphatic regulation in nonmammalian vertebrates.

    PubMed

    Hedrick, Michael S; Hillman, Stanley S; Drewes, Robert C; Withers, Philip C

    2013-08-01

    All vertebrate animals share in common the production of lymph through net capillary filtration from their closed circulatory system into their tissues. The balance of forces responsible for net capillary filtration and lymph formation is described by the Starling equation, but additional factors such as vascular and interstitial compliance, which vary markedly among vertebrates, also have a significant impact on rates of lymph formation. Why vertebrates show extreme variability in rates of lymph formation and how nonmammalian vertebrates maintain plasma volume homeostasis is unclear. This gap hampers our understanding of the evolution of the lymphatic system and its interaction with the cardiovascular system. The evolutionary origin of the vertebrate lymphatic system is not clear, but recent advances suggest common developmental factors for lymphangiogenesis in teleost fishes, amphibians, and mammals with some significant changes in the water-land transition. The lymphatic system of anuran amphibians is characterized by large lymphatic sacs and two pairs of lymph hearts that return lymph into the venous circulation but no lymph vessels per se. The lymphatic systems of reptiles and some birds have lymph hearts, and both groups have extensive lymph vessels, but their functional role in both lymph movement and plasma volume homeostasis is almost completely unknown. The purpose of this review is to present an evolutionary perspective in how different vertebrates have solved the common problem of the inevitable formation of lymph from their closed circulatory systems and to point out the many gaps in our knowledge of this evolutionary progression. PMID:23640588

  16. Evolution of vertebrate opioid receptors

    PubMed Central

    Dreborg, Susanne; Sundström, Görel; Larsson, Tomas A.; Larhammar, Dan

    2008-01-01

    The opioid peptides and receptors have prominent roles in pain transmission and reward mechanisms in mammals. The evolution of the opioid receptors has so far been little studied, with only a few reports on species other than tetrapods. We have investigated species representing a broader range of vertebrates and found that the four opioid receptor types (delta, kappa, mu, and NOP) are present in most of the species. The gene relationships were deduced by using both phylogenetic analyses and chromosomal location relative to 20 neighboring gene families in databases of assembled genomes. The combined results show that the vertebrate opioid receptor gene family arose by quadruplication of a large chromosomal block containing at least 14 other gene families. The quadruplication seems to coincide with, and, therefore, probably resulted from, the two proposed genome duplications in early vertebrate evolution. We conclude that the quartet of opioid receptors was already present at the origin of jawed vertebrates ≈450 million years ago. A few additional opioid receptor gene duplications have occurred in bony fishes. Interestingly, the ancestral receptor gene duplications coincide with the origin of the four opioid peptide precursor genes. Thus, the complete vertebrate opioid system was already established in the first jawed vertebrates. PMID:18832151

  17. 2R and remodeling of vertebrate signal transduction engine

    PubMed Central

    2010-01-01

    Background Whole genome duplication (WGD) is a special case of gene duplication, observed rarely in animals, whereby all genes duplicate simultaneously through polyploidisation. Two rounds of WGD (2R-WGD) occurred at the base of vertebrates, giving rise to an enormous wave of genetic novelty, but a systematic analysis of functional consequences of this event has not yet been performed. Results We show that 2R-WGD affected an overwhelming majority (74%) of signalling genes, in particular developmental pathways involving receptor tyrosine kinases, Wnt and transforming growth factor-β ligands, G protein-coupled receptors and the apoptosis pathway. 2R-retained genes, in contrast to tandem duplicates, were enriched in protein interaction domains and multifunctional signalling modules of Ras and mitogen-activated protein kinase cascades. 2R-WGD had a fundamental impact on the cell-cycle machinery, redefined molecular building blocks of the neuronal synapse, and was formative for vertebrate brains. We investigated 2R-associated nodes in the context of the human signalling network, as well as in an inferred ancestral pre-2R (AP2R) network, and found that hubs (particularly involving negative regulation) were preferentially retained, with high connectivity driving retention. Finally, microarrays and proteomics demonstrated a trend for gradual paralog expression divergence independent of the duplication mechanism, but inferred ancestral expression states suggested preferential subfunctionalisation among 2R-ohnologs (2ROs). Conclusions The 2R event left an indelible imprint on vertebrate signalling and the cell cycle. We show that 2R-WGD preferentially retained genes are associated with higher organismal complexity (for example, locomotion, nervous system, morphogenesis), while genes associated with basic cellular functions (for example, translation, replication, splicing, recombination; with the notable exception of cell cycle) tended to be excluded. 2R-WGD set the stage

  18. UDP xylose synthase 1 is required for morphogenesis and histogenesis of the craniofacial skeleton.

    PubMed

    Eames, B Frank; Singer, Amy; Smith, Gabriel A; Wood, Zachary A; Yan, Yi-Lin; He, Xinjun; Polizzi, Samuel J; Catchen, Julian M; Rodriguez-Mari, Adriana; Linbo, Tor; Raible, David W; Postlethwait, John H

    2010-05-15

    UDP-xylose synthase (Uxs1) is strongly conserved from bacteria to humans, but because no mutation has been studied in any animal, we do not understand its roles in development. Furthermore, no crystal structure has been published. Uxs1 synthesizes UDP-xylose, which initiates glycosaminoglycan attachment to a protein core during proteoglycan formation. Crystal structure and biochemical analyses revealed that an R233H substitution mutation in zebrafish uxs1 alters an arginine buried in the dimer interface, thereby destabilizing and, as enzyme assays show, inactivating the enzyme. Homozygous uxs1 mutants lack Alcian blue-positive, proteoglycan-rich extracellular matrix in cartilages of the neurocranium, pharyngeal arches, and pectoral girdle. Transcripts for uxs1 localize to skeletal domains at hatching. GFP-labeled neural crest cells revealed defective organization and morphogenesis of chondrocytes, perichondrium, and bone in uxs1 mutants. Proteoglycans were dramatically reduced and defectively localized in uxs1 mutants. Although col2a1a transcripts over-accumulated in uxs1 mutants, diminished quantities of Col2a1 protein suggested a role for proteoglycans in collagen secretion or localization. Expression of col10a1, indian hedgehog, and patched was disrupted in mutants, reflecting improper chondrocyte/perichondrium signaling. Up-regulation of sox9a, sox9b, and runx2b in mutants suggested a molecular mechanism consistent with a role for proteoglycans in regulating skeletal cell fate. Together, our data reveal time-dependent changes to gene expression in uxs1 mutants that support a signaling role for proteoglycans during at least two distinct phases of skeletal development. These investigations are the first to examine the effect of mutation on the structure and function of Uxs1 protein in any vertebrate embryos, and reveal that Uxs1 activity is essential for the production and organization of skeletal extracellular matrix, with consequent effects on cartilage

  19. Clinical consequences of vertebral fractures.

    PubMed

    Ross, P D

    1997-08-18

    People with vertebral fractures have greater pain, disability, and healthcare utilization, on average, than those without fractures. Most studies of acute pain and disability have been limited to patients with clinically diagnosed fractures (a subset of all symptomatic patients), representing about one third of all patients with fractures identified radiographically. Acute symptoms vary widely. Some patients experience intolerable pain that can be completely debilitating for several weeks or months, whereas about half of all patients with radiographically identified fractures report having had no symptoms. The reasons for this variability are unknown. Chronic pain and disability among patients with vertebral fractures are significantly greater on average than among people without fractures, even after adjusting for comorbid conditions that are common among the elderly. Similar to acute symptoms, chronic symptoms vary widely and often persist for at least several years. The risk of pain and disability increases progressively with the number and severity of vertebral deformities: the risk is multiplied several times with each additional fracture. On average, physical function is impaired among people with vertebral fractures, whether or not they currently report back pain. Declines in physical function and changes in appearance contribute to social isolation and loss of self-esteem, impairing quality of life. The cumulative impact of vertebral fractures on quality of life may rival that of hip fractures because hip fractures are less frequent and occur later in life. As many as 40% of symptomatic vertebral fractures are initially misdiagnosed, signaling a need for greater awareness among physicians and patients. Prevention of initial vertebral fractures should be actively encouraged; even if the initial fracture is asymptomatic, it indicates a greatly increased risk of subsequent fractures, pain, and physical impairment. PMID:9302895

  20. Specificity protein 7 is not essential for tooth morphogenesis

    PubMed Central

    Clarke, John C.; Bae, Ji-Myung; Adhami, Mitra; Rashid, Harunur; Chen, Haiyan; Napierala, Dobrawa; Gutierrez, Soraya E.; Sinha, Krishna; de Crombrugghe, Benoit; Javed, Amjad

    2014-01-01

    Tooth formation is a multifaceted process involving numerous interactions between oral epithelium and neural crest derived ecto-mesenchyme from morphogenesis to cytodifferentiation. The precise molecular regulator that drives the cyto-differentiation and dynamic cross-talk between the two cell types has yet to be fully understood. Runx2 along with its downstream target Sp7 are essential transcription factors for development of the mineralizing cell types. Global knockout of the Runx2 gene results in an arrest of tooth morphogenesis at the late bud stage. Like Runx2, Sp7-null mutants exhibit peri-natal lethality and are completely devoid of alveolar bone. However, the role of Sp7 in tooth development remains elusive. Here, we report the effects of Sp7 deletion on tooth formation. Surprisingly, tooth morphogenesis progresses normally until the mid bell stage in Sp7-homozygous mutants. Incisors and multi-cusped first and second molars were noted in both littermates. Thus, formation of alveolar bone is not a prerequisite for tooth morphogenesis. Tooth organs of Sp7-null however, were significantly smaller in size when compared to WT. Differentiation of both ameloblasts and odontoblasts was disrupted in Sp7-null mice. Only premature and disorganized ameloblasts and odontoblasts were noted in mutant mice. These data indicate that Sp7 is not required for tooth morphogenesis but is obligatory for the functional maturation of both ameloblasts and odontoblasts. PMID:25158188

  1. Myosin II Dynamics during Embryo Morphogenesis

    NASA Astrophysics Data System (ADS)

    Kasza, Karen

    2013-03-01

    During embryonic morphogenesis, the myosin II motor protein generates forces that help to shape tissues, organs, and the overall body form. In one dramatic example in the Drosophila melanogaster embryo, the epithelial tissue that will give rise to the body of the adult animal elongates more than two-fold along the head-to-tail axis in less than an hour. This elongation is accomplished primarily through directional rearrangements of cells within the plane of the tissue. Just prior to elongation, polarized assemblies of myosin II accumulate perpendicular to the elongation axis. The contractile forces generated by myosin activity orient cell movements along a common axis, promoting local cell rearrangements that contribute to global tissue elongation. The molecular and mechanical mechanisms by which myosin drives this massive change in embryo shape are poorly understood. To investigate these mechanisms, we generated a collection of transgenic flies expressing variants of myosin II with altered motor function and regulation. We found that variants that are predicted to have increased myosin activity cause defects in tissue elongation. Using biophysical approaches, we found that these myosin variants also have decreased turnover dynamics within cells. To explore the mechanisms by which molecular-level myosin dynamics are translated into tissue-level elongation, we are using time-lapse confocal imaging to observe cell movements in embryos with altered myosin activity. We are utilizing computational approaches to quantify the dynamics and directionality of myosin localization and cell rearrangements. These studies will help elucidate how myosin-generated forces control cell movements within tissues. This work is in collaboration with J. Zallen at the Sloan-Kettering Institute.

  2. [The phylogenetic role of ontogenies (recapitulation and morphogenesis)].

    PubMed

    Mamkaev, Iu V

    2009-01-01

    Different approaches to evolutionary interpretation of ontogenies are compared, with special emphasis on the evolutionary role of morphogenetic mechanisms (construction technologies) substantially affecting the structure of definitive forms: they largely determine the structural characteristics of organs, types of anatomical and histological systems, and specificity of symmetry of organisms and their parts. The role of cellular morphogenesis inherited from protozoic ancestors in the morphogenesis of multicellular organisms is demonstrated. Two main ways of improving morphogeneses are considered, based on epithelial morphogenesis and early determined few-celled primordial. On the one hand, the phylogenetic role of archallaxes and deviations is emphasized, these events often switching evolution to a fundamentally new direction. On the other hand, many characteristics of developmental stages are explainable by rationalization of morphogeneses and do not recapitulate ancestral forms, which should be taken into consideration in phylogenetic interpretation of embryogeneses; in particular, this applies to interpretation of axial relationships. PMID:19396969

  3. The Fog signaling pathway: Insights into signaling in morphogenesis

    PubMed Central

    Manning, Alyssa J.; Rogers, Stephen L.

    2014-01-01

    Epithelia form the building blocks of many tissue and organ types. Epithelial cells often form a contiguous 2-dimensional sheet that is held together by strong adhesions. The mechanical properties conferred by these adhesions allow the cells to undergo dramatic three-dimensional morphogenetic movements while maintaining cell–cell contacts during embryogenesis and post-embryonic development. The Drosophila Folded gastrulation pathway triggers epithelial cell shape changes that drive gastrulation and tissue folding and is one of the most extensively studied examples of epithelial morphogenesis. This pathway has yielded key insights into the signaling mechanisms and cellular machinery involved in epithelial remodeling. In this review, we discuss principles of morphogenesis and signaling that have been discovered through genetic and cell biological examination of this pathway. We also consider various regulatory mechanisms and the system's relevance to mammalian development. We propose future directions that will continue to broaden our knowledge of morphogenesis across taxa. PMID:25127992

  4. Medical treatment of vertebral osteoporosis.

    PubMed

    Lippuner, K

    2003-10-01

    Although osteoporosis is a systemic disease, vertebral fractures due to spinal bone loss are a frequent, sometimes early and often neglected complication of the disease, generally associated with considerable disability and pain. As osteoporotic vertebral fractures are an important predictor of future fracture risk, including at the hip, medical management is targeted at reducing fracture risk. A literature search for randomized, double-blind, prospective, controlled clinical studies addressing medical treatment possibilities of vertebral fractures in postmenopausal Caucasian women was performed on the leading medical databases. For each publication, the number of patients with at least one new vertebral fracture and the number of randomized patients by treatment arm was retrieved. The relative risk (RR) and the number needed to treat (NNT, i.e. the number of patients to be treated to avoid one radiological vertebral fracture over the duration of the study), together with the respective 95% confidence intervals (95%CI) were calculated for each study. Treatment of steroid-induced osteoporosis and treatment of osteoporosis in men were reviewed separately, based on the low number of publications available. Forty-five publications matched with the search criteria, allowing for analysis of 15 different substances tested regarding their anti-fracture efficacy at the vertebral level. Bisphosphonates, mainly alendronate and risedronate, were reported to have consistently reduced the risk of a vertebral fracture over up to 50 months of treatment in four (alendronate) and two (risedronate) publications. Raloxifene reduced vertebral fracture risk in one study over 36 months, which was confirmed by 48 months' follow-up data. Parathormone (PTH) showed a drastic reduction in vertebral fracture risk in early studies, while calcitonin may also be a treatment option to reduce fracture risk. For other substances published data are conflicting (calcitriol, fluoride) or insufficient

  5. Ontogenetic cell death and phagocytosis in the visual system of vertebrates.

    PubMed

    Francisco-Morcillo, Javier; Bejarano-Escobar, Ruth; Rodríguez-León, Joaquín; Navascués, Julio; Martín-Partido, Gervasio

    2014-10-01

    Programmed cell death (PCD), together with cell proliferation, cell migration, and cell differentiation, is an essential process during development of the vertebrate nervous system. The visual system has been an excellent model on which to investigate the mechanisms involved in ontogenetic cell death. Several phases of PCD have been reported to occur during visual system ontogeny. During these phases, comparative analyses demonstrate that dying cells show similar but not identical spatiotemporally restricted patterns in different vertebrates. Additionally, the chronotopographical coincidence of PCD with the entry of specialized phagocytes in some regions of the developing vertebrate visual system suggests that factors released from degenerating cells are involved in the cell migration of macrophages and microglial cells. Contradicting this hypothesis however, in many cases the cell corpses generated during degeneration are rapidly phagocytosed by neighboring cells, such as neuroepithelial cells or Müller cells. In this review, we describe the occurrence and the sites of PCD during the morphogenesis and differentiation of the retina and optic pathways of different vertebrates, and discuss the possible relationship between PCD and phagocytes during ontogeny.

  6. Neuropilin-2 promotes branching morphogenesis in the mouse mammary gland.

    PubMed

    Goel, Hira Lal; Bae, Donggoo; Pursell, Bryan; Gouvin, Lindsey M; Lu, Shaolei; Mercurio, Arthur M

    2011-07-01

    Although the neuropilins were characterized as semaphorin receptors that regulate axon guidance, they also function as vascular endothelial growth factor (VEGF) receptors and contribute to the development of other tissues. Here, we assessed the role of NRP2 in mouse mammary gland development based on our observation that NRP2 is expressed preferentially in the terminal end buds of developing glands. A floxed NRP2 mouse was bred with an MMTV-Cre strain to generate a mammary gland-specific knockout of NRP2. MMTV-Cre;NRP2(loxP/loxP) mice exhibited significant defects in branching morphogenesis and ductal outgrowth compared with either littermate MMTV-Cre;NRP2(+/loxP) or MMTV-Cre mice. Mechanistic insight into this morphological defect was obtained from a mouse mammary cell line in which we observed that VEGF(165), an NRP2 ligand, induces branching morphogenesis in 3D cultures and that branching is dependent upon NRP2 as shown using shRNAs and a function-blocking antibody. Epithelial cells in the mouse mammary gland express VEGF, supporting the hypothesis that this NRP2 ligand contributes to mammary gland morphogenesis. Importantly, we demonstrate that VEGF and NRP2 activate focal adhesion kinase (FAK) and promote FAK-dependent branching morphogenesis in vitro. The significance of this mechanism is substantiated by our finding that FAK activation is diminished significantly in developing MMTV-Cre;NRP2(loxP/loxP) mammary glands compared with control glands. Together, our data reveal a VEGF/NRP2/FAK signaling axis that is important for branching morphogenesis and mammary gland development. In a broader context, our data support an emerging hypothesis that directional outgrowth and branching morphogenesis in a variety of tissues are influenced by signals that were identified initially for their role in axon guidance.

  7. Turing's next steps: the mechanochemical basis of morphogenesis.

    PubMed

    Howard, Jonathon; Grill, Stephan W; Bois, Justin S

    2011-06-01

    Nearly 60 years ago, Alan Turing showed theoretically how two chemical species, termed morphogens, diffusing and reacting with each other can generate spatial patterns. Diffusion plays a crucial part in transporting chemical signals through space to establish the length scale of the pattern. When coupled to chemical reactions, mechanical processes - forces and flows generated by motor proteins - can also define length scales and provide a mechanochemical basis for morphogenesis. forces and flows generated by motor proteins - can also define length scales and provide a mechanochemical basis for morphogenesis.

  8. Turing's next steps: the mechanochemical basis of morphogenesis.

    PubMed

    Howard, Jonathon; Grill, Stephan W; Bois, Justin S

    2011-06-01

    Nearly 60 years ago, Alan Turing showed theoretically how two chemical species, termed morphogens, diffusing and reacting with each other can generate spatial patterns. Diffusion plays a crucial part in transporting chemical signals through space to establish the length scale of the pattern. When coupled to chemical reactions, mechanical processes - forces and flows generated by motor proteins - can also define length scales and provide a mechanochemical basis for morphogenesis. forces and flows generated by motor proteins - can also define length scales and provide a mechanochemical basis for morphogenesis. PMID:21602907

  9. Quantitative approaches to uncover physical mechanisms of tissue morphogenesis

    PubMed Central

    Gleghorn, Jason P.; Manivannan, Sriram; Nelson, Celeste M.

    2013-01-01

    Morphogenesis, the creation of tissue and organ architecture, is a series of complex and dynamic processes driven by genetic programs, microenvironmental cues, and intercellular interactions. Elucidating the physical mechanisms that generate tissue form is key to understanding development, disease, and the strategies needed for regenerative therapies. Advancements in imaging technologies, genetic recombination techniques, laser ablation, and microfabricated tissue models have enabled quantitative descriptions of the cellular motions and tissue deformations and stresses with unprecedented temporal and spatial resolution. Using these data synergistically with increasingly more sophisticated physical, mathematical, and computational models will unveil the physical mechanisms that drive morphogenesis. PMID:23647971

  10. Bone morphogenetic protein signaling promotes morphogenesis of blood vessels, wound epidermis, and actinotrichia during fin regeneration in zebrafish.

    PubMed

    Thorimbert, Valentine; König, Désirée; Marro, Jan; Ruggiero, Florence; Jaźwińska, Anna

    2015-10-01

    Zebrafish fin regeneration involves initial formation of the wound epidermis and the blastema, followed by tissue morphogenesis. The mechanisms coordinating differentiation of distinct tissues of the regenerate are poorly understood. Here, we applied pharmacologic and transgenic approaches to address the role of bone morphogenetic protein (BMP) signaling during fin restoration. To map the BMP transcriptional activity, we analyzed the expression of the evolutionarily conserved direct phospho-Smad1 target gene, id1, and its homologs id2a and id3. This analysis revealed the BMP activity in the distal blastema, wound epidermis, osteoblasts, and blood vessels of the regenerate. Blocking the BMP function with a selective chemical inhibitor of BMP type I receptors, DMH1, suppressed id1 and id3 expression and arrested regeneration after blastema formation. We identified several previously uncharacterized functions of BMP during fin regeneration. Specifically, BMP signaling is required for remodeling of plexus into structured blood vessels in the rapidly growing regenerate. It organizes the wound epithelium by triggering wnt5b expression and promoting Collagen XIV-A deposition into the basement membrane. BMP represents the first known signaling that induces actinotrichia formation in the regenerate. Our data reveal a multifaceted role of BMP for coordinated morphogenesis of distinct tissues during regeneration of a complex vertebrate appendage.

  11. Role of cranial neural crest cells in visceral arch muscle positioning and morphogenesis in the Mexican axolotl, Ambystoma mexicanum.

    PubMed

    Ericsson, Rolf; Cerny, Robert; Falck, Pierre; Olsson, Lennart

    2004-10-01

    The role of cranial neural crest cells in the formation of visceral arch musculature was investigated in the Mexican axolotl, Ambystoma mexicanum. DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine, perchlorate) labeling and green fluorescent protein (GFP) mRNA injections combined with unilateral transplantations of neural folds showed that neural crest cells contribute to the connective tissues but not the myofibers of developing visceral arch muscles in the mandibular, hyoid, and branchial arches. Extirpations of individual cranial neural crest streams demonstrated that neural crest cells are necessary for correct morphogenesis of visceral arch muscles. These do, however, initially develop in their proper positions also in the absence of cranial neural crest. Visceral arch muscles forming in the absence of neural crest cells start to differentiate at their origins but fail to extend toward their insertions and may have a frayed appearance. Our data indicate that visceral arch muscle positioning is controlled by factors that do not have a neural crest origin. We suggest that the cranial neural crest-derived connective tissues provide directional guidance important for the proper extension of the cranial muscles and the subsequent attachment to the insertion on the correct cartilage. In a comparative context, our data from the Mexican axolotl support the view that the cranial neural crest plays a fundamental role in the development of not only the skeleton of the vertebrate head but also in the morphogenesis of the cranial muscles and that this might be a primitive feature of cranial development in vertebrates. PMID:15366001

  12. Learning about Vertebrate Limb Development

    ERIC Educational Resources Information Center

    Liang, Jennifer O.; Noll, Matthew; Olsen, Shayna

    2014-01-01

    We have developed an upper-level undergraduate laboratory exercise that enables students to replicate a key experiment in developmental biology. In this exercise, students have the opportunity to observe live chick embryos and stain the apical ectodermal ridge, a key tissue required for development of the vertebrate limb. Impressively, every…

  13. Resolving Conflicts: Modeling Genetic Control of Plant Morphogenesis.

    PubMed

    Coen, Enrico; Rebocho, Alexandra B

    2016-09-26

    Computational modeling of tissue morphogenesis reveals how spatiotemporal patterns of gene activity control tissue shape by introducing several types of tissue conflict. These conflicts reflect genetic modulation of processes that influence the cellular mechanical properties and may underlie the enormous diversity of forms that have evolved in plants and animals. PMID:27676429

  14. Primary Cilia Regulate Branching Morphogenesis During Mammary Gland Development

    PubMed Central

    McDermott, Kimberly M.; Liu, Bob Y.; Tlsty, Thea D.; Pazour, Gregory J.

    2010-01-01

    Summary During mammary gland development an epithelial bud undergoes branching morphogenesis to expand into a continuous tree-like network of branched ducts [1]. The process involves multiple cell types that are coordinated by hormones and growth factors coupled with signaling events including Wnt and Hedgehog [2-5]. Primary cilia play key roles in the development of many organs by coordinating extracellular signaling (Wnt, Hedgehog) with cellular physiology [6-8]. During mammary development, we find cilia on luminal epithelial, myoepithelial and stromal cells during early branching morphogenesis when epithelial ducts extend into the fat pad and undergo branching morphogenesis. When branching is complete, cilia disappear from luminal epithelial cells but remain on myoepithelial and stromal cells. Ciliary dysfunction caused by intraflagellar transport (IFT) defects results in branching defects. These include decreased ductal extension and decreased secondary and tertiary branching along with reduced lobular-alveolar development during pregnancy and lactation. We find increased canonical Wnt and decreased Hedgehog signaling in the mutant glands, which is consistent with the role of cilia in regulating these pathways [6-11]. In mammary gland and other organs, increased canonical Wnt [12-14] and decreased Hedgehog [15, 16] signaling decreases branching morphogenesis suggesting that Wnt and Hedgehog signaling connect ciliary dysfunction to branching defects. PMID:20381354

  15. Epithelial morphogenesis: the mouse eye as a model system.

    PubMed

    Chauhan, Bharesh; Plageman, Timothy; Lou, Ming; Lang, Richard

    2015-01-01

    Morphogenesis is the developmental process by which tissues and organs acquire the shape that is critical to their function. Here, we review recent advances in our understanding of the mechanisms that drive morphogenesis in the developing eye. These investigations have shown that regulation of the actin cytoskeleton is central to shaping the presumptive lens and retinal epithelia that are the major components of the eye. Regulation of the actin cytoskeleton is mediated by Rho family GTPases, by signaling pathways and indirectly, by transcription factors that govern the expression of critical genes. Changes in the actin cytoskeleton can shape cells through the generation of filopodia (that, in the eye, connect adjacent epithelia) or through apical constriction, a process that produces a wedge-shaped cell. We have also learned that one tissue can influence the shape of an adjacent one, probably by direct force transmission, in a process we term inductive morphogenesis. Though these mechanisms of morphogenesis have been identified using the eye as a model system, they are likely to apply broadly where epithelia influence the shape of organs during development.

  16. Subtractive transcriptomics : establishing polarity drives human endothelial morphogenesis

    SciTech Connect

    Glesne, D. A.; Zhang, W.; Mandava, S.; Ursos, L.; Buell, M. E.; Makowski, L.; Rodi, D. J.; Biosciences Division

    2006-04-15

    Although investigations of mature normal and tumor-derived capillaries have resulted in characterization of these structures at the phenotypic level, less is known regarding the initial molecular cues for cellular assembly of endothelial cells into human capillaries. Here, we employ a novel combination of microenvironmental manipulation and microarray data filtration over narrowly delineated temporal data series to identify the morphogenesis component apart from the proliferation component, as pooled human microvascular-derived endothelial cells are induced to form capillary-like structures in vitro in a murine tumor-derived matrix. The 217 morphogenesis-specific genes identified using this subtractive transcriptomics approach are mostly independent of the angiogenic proteins currently used as therapeutic targets for aberrant angiogenesis. Quantitative real-time PCR was used to validate 20% of these transcripts. Immunofluorescent analysis of proliferating and tube-forming cells validates at the protein level the morphogenesis-specific expression pattern of 16 of the 217 gene products identified. The transcripts that are selectively up-regulated in tube-forming endothelial cells reveal a temporal expression pattern of genes primarily associated with intracellular trafficking, guided migration, cytoskeletal reorganization, cellular adhesion, and proliferation inhibition. These data show that a sequential upregulation of genes that establish and maintain polarity occurs during migration and morphogenesis of in vitro human endothelial cells undergoing tubulogenesis; some of which may well be effective as novel antiangiogenic drug targets.

  17. AHR signaling in prostate growth, morphogenesis, and disease

    PubMed Central

    Vezina, Chad M.; Lin, Tien-Min; Peterson, Richard E.

    2010-01-01

    Most evidence of aryl hydrocarbon receptor (AHR) signaling in prostate growth, morphogenesis, and disease stems from research using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to pharmacologically activate the AHR at various stages of development. This review discusses effects of TCDD on prostate morphogenesis and highlights interactions between AHR and other signaling pathways during normal and aberrant prostate growth. Although AHR signaling modulates estrogen and androgen signaling in other tissues, crosstalk between these steroid hormone receptors and AHR signaling cannot account for actions of TCDD on prostate morphogenesis. Instead, the AHR appears to act within a cooperative framework of developmental signals to regulate timing and patterning of prostate growth. Inappropriate activation of AHR signaling as a result of early life TCDD exposure disrupts the balance of these signals, impairs prostate morphogenesis, and has an imprinting effect on the developing prostate that predisposes to prostate disease in adulthood. Mechanisms of AHR signaling in prostate growth and disease are only beginning to be unraveled and recent studies have revealed its interactions with WNT5A, retinoic acid, fibroblast growth factor 10, and vascular endothelial growth factor signaling pathways. PMID:18977204

  18. Endogenous patterns of mechanical stress are required for branching morphogenesis

    PubMed Central

    Gjorevski, Nikolce; Nelson, Celeste M.

    2011-01-01

    Spatial patterning of cell behaviors establishes the regional differences within tissues that collectively develop branched organs into their characteristic treelike shapes. Here we show that the pattern of branching morphogenesis of three-dimensional (3D) engineered epithelial tissues is controlled in part by gradients of endogenous mechanical stress. We used microfabrication to build model mammary epithelial tissues of defined geometry that branched in a stereotyped pattern when induced with growth factors. Branches initiated from sites of high mechanical stress within the tissues, as predicted numerically and measured directly using 3D traction force microscopy. Branch sites were defined by activation of focal adhesion kinase (FAK), inhibition of which disrupted morphogenesis. Stress, FAK activation, and branching were all altered by manipulating cellular contractility, matrix stiffness, intercellular cohesion and tissue geometry. These data suggest that the pattern and magnitude of mechanical stress across epithelial tissues cooperate with biochemical signals to specify branching pattern. Insight, innovation, integration Morphogenesis is ultimately a physical process wherein tissues are sculpted into their final three-dimensional (3D) patterns. Mechanical stresses from the microenvironment can also play regulatory roles, but their influence on pattern is difficult to ascertain in 3D systems in vivo. Here we integrate 3D microscale engineered tissues with insight from biological mechanics to understand the role of endogenous mechanical stresses in patterning tissue development. The innovation lies in the use of numerical modeling to design experiments that can predict the stress distribution and resulting morphogenesis of model tissues. PMID:20717570

  19. Rap1 GTPase is required for mouse lens epithelial maintenance and morphogenesis

    PubMed Central

    Maddala, Rupalatha; Nagendran, Tharkika; Lang, Richard A.; Morozov, Alexei; Rao, Ponugoti V.

    2015-01-01

    Rap1, a Ras-like small GTPase, plays a crucial role in cell-matrix adhesive interactions, cell-cell junction formation, cell polarity and migration. The role of Rap1 in vertebrate organ development and tissue architecture, however, remains elusive. We addressed this question in a mouse lens model system using a conditional gene targeting approach. While individual germline deficiency of either Rap1a or Rap1b did not cause overt defects in mouse lens, conditional double deficiency (Rap1 cKO) prior to lens placode formation led to an ocular phenotype including microphthalmia and lens opacification in embryonic mice. The embryonic Rap1 cKO mouse lens exhibited striking defects including loss of E-cadherin- and ZO-1-based cell-cell junctions, disruption of paxillin and β1-integrin-based cell adhesive interactions along with abnormalities in cell shape and apical-basal polarity of epithelium. These epithelial changes were accompanied by increased levels of α-smooth muscle actin, vimentin and N-cadherin, and expression of transcriptional suppressors of E-cadherin (Snai1, Slug and Zeb2), and a mesenchymal metabolic protein (Dihydropyrimidine dehydrogenase). Additionally, while lens differentiation was not overtly affected, increased apoptosis and dysregulated cell cycle progression were noted in epithelium and fibers in Rap1 cKO mice. Collectively these observations uncover a requirement for Rap1 in maintenance of lens epithelial phenotype and morphogenesis. PMID:26212757

  20. Drosophila CK1-γ, gilgamesh, controls PCP-mediated morphogenesis through regulation of vesicle trafficking

    PubMed Central

    Gault, William J.; Olguin, Patricio; Weber, Ursula

    2012-01-01

    Cellular morphogenesis, including polarized outgrowth, promotes tissue shape and function. Polarized vesicle trafficking has emerged as a fundamental mechanism by which protein and membrane can be targeted to discrete subcellular domains to promote localized protrusions. Frizzled (Fz)/planar cell polarity (PCP) signaling orchestrates cytoskeletal polarization and drives morphogenetic changes in such contexts as the vertebrate body axis and external Drosophila melanogaster tissues. Although regulation of Fz/PCP signaling via vesicle trafficking has been identified, the interplay between the vesicle trafficking machinery and downstream terminal PCP-directed processes is less established. In this paper, we show that Drosophila CK1-γ/gilgamesh (gish) regulates the PCP-associated process of trichome formation through effects on Rab11-mediated vesicle recycling. Although the core Fz/PCP proteins dictate prehair formation broadly, CK1-γ/gish restricts nucleation to a single site. Moreover, CK1-γ/gish works in parallel with the Fz/PCP effector multiple wing hairs, which restricts prehair formation along the perpendicular axis to Gish. Our findings suggest that polarized Rab11-mediated vesicle trafficking regulated by CK1-γ is required for PCP-directed processes. PMID:22391037

  1. Drosophila CK1-γ, gilgamesh, controls PCP-mediated morphogenesis through regulation of vesicle trafficking.

    PubMed

    Gault, William J; Olguin, Patricio; Weber, Ursula; Mlodzik, Marek

    2012-03-01

    Cellular morphogenesis, including polarized outgrowth, promotes tissue shape and function. Polarized vesicle trafficking has emerged as a fundamental mechanism by which protein and membrane can be targeted to discrete subcellular domains to promote localized protrusions. Frizzled (Fz)/planar cell polarity (PCP) signaling orchestrates cytoskeletal polarization and drives morphogenetic changes in such contexts as the vertebrate body axis and external Drosophila melanogaster tissues. Although regulation of Fz/PCP signaling via vesicle trafficking has been identified, the interplay between the vesicle trafficking machinery and downstream terminal PCP-directed processes is less established. In this paper, we show that Drosophila CK1-γ/gilgamesh (gish) regulates the PCP-associated process of trichome formation through effects on Rab11-mediated vesicle recycling. Although the core Fz/PCP proteins dictate prehair formation broadly, CK1-γ/gish restricts nucleation to a single site. Moreover, CK1-γ/gish works in parallel with the Fz/PCP effector multiple wing hairs, which restricts prehair formation along the perpendicular axis to Gish. Our findings suggest that polarized Rab11-mediated vesicle trafficking regulated by CK1-γ is required for PCP-directed processes. PMID:22391037

  2. A case of split notochord syndrome with congenital ileal atresia, the total absence of a colon, and a dorsal enteric cyst communicating to the retroperitoneal isolated ceca with a vesical fistula.

    PubMed

    Asagiri, Kimio; Yagi, Minoru; Tanaka, Yoshiaki; Akaiwa, Masao; Asakawa, Takahiro; Kaida, Akiko; Kobayashi, Hidefumi; Tanaka, Hiroaki

    2008-09-01

    Split notochord syndrome (SNS) is an extremely rare anomaly. This report presents the case of a male infant with SNS associated with congenital ileal atresia and a dorsal enteric cyst communicating to the retroperitoneal isolated ceca with a vesical fistula. Dorsal fistulography and vesicography were useful and essential for the detailed study of the topology in this patient. The embryological mechanism and etiologic theories are discussed with a review of 19 cases reported in the literature.

  3. Fibronectin Deposition Participates in Extracellular Matrix Assembly and Vascular Morphogenesis

    PubMed Central

    Hielscher, Abigail; Ellis, Kim; Qiu, Connie; Porterfield, Josh; Gerecht, Sharon

    2016-01-01

    The extracellular matrix (ECM) has been demonstrated to facilitate angiogenesis. In particular, fibronectin has been documented to activate endothelial cells, resulting in their transition from a quiescent state to an active state in which the cells exhibit enhanced migration and proliferation. The goal of this study is to examine the role of polymerized fibronectin during vascular tubulogenesis using a 3 dimensional (3D) cell-derived de-cellularized matrix. A fibronectin-rich 3D de-cellularized ECM was used as a scaffold to study vascular morphogenesis of endothelial cells (ECs). Confocal analyses of several matrix proteins reveal high intra- and extra-cellular deposition of fibronectin in formed vascular structures. Using a small peptide inhibitor of fibronectin polymerization, we demonstrate that inhibition of fibronectin fibrillogenesis in ECs cultured atop de-cellularized ECM resulted in decreased vascular morphogenesis. Further, immunofluorescence and ultrastructural analyses reveal decreased expression of stromal matrix proteins in the absence of polymerized fibronectin with high co-localization of matrix proteins found in association with polymerized fibronectin. Evaluating vascular kinetics, live cell imaging showed that migration, migration velocity, and mean square displacement, are disrupted in structures grown in the absence of polymerized fibronectin. Additionally, vascular organization failed to occur in the absence of a polymerized fibronectin matrix. Consistent with these observations, we tested vascular morphogenesis following the disruption of EC adhesion to polymerized fibronectin, demonstrating that block of integrins α5β1 and αvβ3, abrogated vascular morphogenesis. Overall, fibronectin deposition in a 3D cell-derived de-cellularized ECM appears to be imperative for matrix assembly and vascular morphogenesis. PMID:26811931

  4. Morphological castes in a vertebrate.

    PubMed

    O'Riain, M J; Jarvis, J U; Alexander, R; Buffenstein, R; Peeters, C

    2000-11-21

    Morphological specialization for a specific role has, until now, been assumed to be restricted to social invertebrates. Herein we show that complete physical dimorphism has evolved between reproductives and helpers in the eusocial naked mole-rat. Dimorphism is a consequence of the lumbar vertebrae lengthening after the onset of reproduction in females. This is the only known example of morphological castes in a vertebrate and is distinct from continuous size variation between breeders and helpers in other species of cooperatively breeding vertebrates. The evolution of castes in a mammal and insects represents a striking example of convergent evolution for enhanced fecundity in societies characterized by high reproductive skew. Similarities in the selective environment between naked mole-rats and eusocial insect species highlight the selective conditions under which queen/worker castes are predicted to evolve in animal societies.

  5. Climate change and marine vertebrates.

    PubMed

    Sydeman, William J; Poloczanska, Elvira; Reed, Thomas E; Thompson, Sarah Ann

    2015-11-13

    Climate change impacts on vertebrates have consequences for marine ecosystem structures and services. We review marine fish, mammal, turtle, and seabird responses to climate change and discuss their potential for adaptation. Direct and indirect responses are demonstrated from every ocean. Because of variation in research foci, observed responses differ among taxonomic groups (redistributions for fish, phenology for seabirds). Mechanisms of change are (i) direct physiological responses and (ii) climate-mediated predator-prey interactions. Regional-scale variation in climate-demographic functions makes range-wide population dynamics challenging to predict. The nexus of metabolism relative to ecosystem productivity and food webs appears key to predicting future effects on marine vertebrates. Integration of climate, oceanographic, ecosystem, and population models that incorporate evolutionary processes is needed to prioritize the climate-related conservation needs for these species. PMID:26564847

  6. Climate change and marine vertebrates.

    PubMed

    Sydeman, William J; Poloczanska, Elvira; Reed, Thomas E; Thompson, Sarah Ann

    2015-11-13

    Climate change impacts on vertebrates have consequences for marine ecosystem structures and services. We review marine fish, mammal, turtle, and seabird responses to climate change and discuss their potential for adaptation. Direct and indirect responses are demonstrated from every ocean. Because of variation in research foci, observed responses differ among taxonomic groups (redistributions for fish, phenology for seabirds). Mechanisms of change are (i) direct physiological responses and (ii) climate-mediated predator-prey interactions. Regional-scale variation in climate-demographic functions makes range-wide population dynamics challenging to predict. The nexus of metabolism relative to ecosystem productivity and food webs appears key to predicting future effects on marine vertebrates. Integration of climate, oceanographic, ecosystem, and population models that incorporate evolutionary processes is needed to prioritize the climate-related conservation needs for these species.

  7. Extraneural Glioblastoma Multiforme Vertebral Metastasis

    PubMed Central

    Goodwin, C. Rory; Liang, Lydia; Abu-Bonsrah, Nancy; Hdeib, Alia; Elder, Benjamin D.; Kosztowski, Thomas; Bettegowda, Chetan; Laterra, John; Burger, Peter; Sciubba, Daniel M.

    2016-01-01

    Glioblastoma multiforme (GBM) is the most common malignant central nervous system tumor; however, extraneural metastasis is uncommon. Of those that metastasize extraneurally, metastases to the vertebral bodies represent a significant proportion. We present a review of 28 cases from the published literature of GBM metastasis to the vertebra. The mean age at presentation was 38.4 years with an average overall survival of 26 months. Patients were either asymptomatic with metastasis discovered at autopsy or presented with varying degrees of pain, weakness of the extremities, or other neurologic deficits. Of the cases that included the time to spinal metastasis, the average time was 26.4 months with a reported survival of 10 months after diagnosis of vertebral metastasis. A significant number of patients had no treatments for their spinal metastasis, although the intracranial lesions were treated extensively with surgery and/or adjuvant therapy. With increasing incremental gains in the survival of patients with GBM, clinicians will encounter patients with extracranial metastasis. As such, this review presents timely information concerning the presentation and outcomes of patients with vertebral metastasis. PMID:26704201

  8. Extraneural Glioblastoma Multiforme Vertebral Metastasis.

    PubMed

    Goodwin, C Rory; Liang, Lydia; Abu-Bonsrah, Nancy; Hdeib, Alia; Elder, Benjamin D; Kosztowski, Thomas; Bettegowda, Chetan; Laterra, John; Burger, Peter; Sciubba, Daniel M

    2016-05-01

    Glioblastoma multiforme (GBM) is the most common malignant central nervous system tumor; however, extraneural metastasis is uncommon. Of those that metastasize extraneurally, metastases to the vertebral bodies represent a significant proportion. We present a review of 28 cases from the published literature of GBM metastasis to the vertebra. The mean age at presentation was 38.4 years with an average overall survival of 26 months. Patients were either asymptomatic with metastasis discovered at autopsy or presented with varying degrees of pain, weakness of the extremities, or other neurologic deficits. Of the cases that included the time to spinal metastasis, the average time was 26.4 months with a reported survival of 10 months after diagnosis of vertebral metastasis. A significant number of patients had no treatments for their spinal metastasis, although the intracranial lesions were treated extensively with surgery and/or adjuvant therapy. With increasing incremental gains in the survival of patients with GBM, clinicians will encounter patients with extracranial metastasis. As such, this review presents timely information concerning the presentation and outcomes of patients with vertebral metastasis. PMID:26704201

  9. Bilateral mechanical rotational vertebral artery occlusion.

    PubMed

    Dargon, Phong T; Liang, Conrad W; Kohal, Anmol; Dogan, Aclan; Barnwell, Stanley L; Landry, Gregory J

    2013-10-01

    Rotational vertebral artery occlusion, or bow hunter's stroke, is reversible, positional symptomatic vertebrobasilar ischemia. The typical mechanism of action is obstruction of a dominant vertebral artery with contralateral head rotation in the setting of baseline ipsilateral vertebral artery stenosis or occlusion. Here we present a rare case of mechanical occlusion of bilateral patent vertebral arteries manifesting as near syncope with rightward head rotation. Diagnostic cerebral angiography showed dynamic right C5 vertebral occlusion and left C2 vertebral occlusion. The patient underwent right C4/5 transverse process decompression. Postoperative angiogram showed patent flow through the right vertebral artery in neutral position and with head turn with resultant resolution of symptoms. PMID:23465174

  10. Morphogenesis of the axolotl pronephric duct: a model system for the study of cell migration in vivo.

    PubMed

    Drawbridge, J; Steinberg, M S

    1996-08-01

    Pronephric duct (PND) morphogenesis is a critical early event in the development of the vertebrate excretory system. This structure is the exit channel for both pronephric and mesonephric filtrate, forms the ureteric bud of the metanephros and gives rise to the ductus deferens of the testis. In addition, the PND and ureteric bud epithelia induce terminal differentiation of the mesonephric and metanephric mesenchyme, respectively. Elongation of the PND in all vertebrates involves active cell migration of the primordium. In urodele embryos--unlike in some anuran, avian and mammalian embryos--elongation of the PND occurs solely by cell migration. In the axolotl embryo, the PND primordium segregates as an ovoid tissue mass from the anterodorsal flank mesoderm directly beneath somites 3-7. The primordium then extends caudally along the ventral border of the developing somites until it reaches the cloaca. The ease with which these embryos can be manipulated microsurgically makes the PND system ideal for the study of the mechanisms controlling cell migration in vivo. This review summarizes the progress that has been made in characterizing the environmental cues and the cell surface recognition systems that drive this tightly regulated migration event. PMID:8877443

  11. Exo70 Generates Membrane Curvature for Morphogenesis and Cell Migration

    PubMed Central

    Zhao, Yuting; Liu, Jianglan; Yang, Changsong; Capraro, Benjamin R.; Baumgart, Tobias; Bradley, Ryan P.; Ramakrishnan, N.; Xu, Xiaowei; Radhakrishnan, Ravi; Svitkina, Tatyana; Guo, Wei

    2013-01-01

    Dynamic shape changes of the plasma membrane are fundamental to many processes ranging from morphogenesis and cell migration to phagocytosis and viral propagation. Here we demonstrate that Exo70, a component of the exocyst complex, induces tubular membrane invaginations towards the lumen of synthetic vesicles in vitro and generates protrusions on the surface of cells. Biochemical analyses using Exo70 mutants and independent molecular dynamics simulations based on Exo70 structure demonstrate that Exo70 generates negative membrane curvature through an oligomerization-based mechanism. In cells, the membrane-deformation function of Exo70 is required for protrusion formation and directional cell migration. Exo70 thus represents a membrane-bending protein that may couple actin dynamics and plasma membrane remodeling for morphogenesis. PMID:23948253

  12. Testing Turing's theory of morphogenesis in chemical cells.

    PubMed

    Tompkins, Nathan; Li, Ning; Girabawe, Camille; Heymann, Michael; Ermentrout, G Bard; Epstein, Irving R; Fraden, Seth

    2014-03-25

    Alan Turing, in "The Chemical Basis of Morphogenesis" [Turing AM (1952) Philos Trans R Soc Lond 237(641):37-72], described how, in circular arrays of identical biological cells, diffusion can interact with chemical reactions to generate up to six periodic spatiotemporal chemical structures. Turing proposed that one of these structures, a stationary pattern with a chemically determined wavelength, is responsible for differentiation. We quantitatively test Turing's ideas in a cellular chemical system consisting of an emulsion of aqueous droplets containing the Belousov-Zhabotinsky oscillatory chemical reactants, dispersed in oil, and demonstrate that reaction-diffusion processes lead to chemical differentiation, which drives physical morphogenesis in chemical cells. We observe five of the six structures predicted by Turing. In 2D hexagonal arrays, a seventh structure emerges, incompatible with Turing's original model, which we explain by modifying the theory to include heterogeneity.

  13. Multi-scale mechanics from molecules to morphogenesis

    PubMed Central

    Davidson, Lance; von Dassow, Michelangelo; Zhou, Jian

    2009-01-01

    Dynamic mechanical processes shape the embryo and organs during development. Little is understood about the basic physics of these processes, what forces are generated, or how tissues resist or guide those forces during morphogenesis. This review offers an outline of some of the basic principles of biomechanics, provides working examples of biomechanical analyses of developing embryos, and reviews the role of structural proteins in establishing and maintaining the mechanical properties of embryonic tissues. Drawing on examples we highlight the importance of investigating mechanics at multiple scales from milliseconds to hours and from individual molecules to whole embryos. Lastly, we pose a series of questions that will need to be addressed if we are to understand the larger integration of molecular and physical mechanical processes during morphogenesis and organogenesis. PMID:19394436

  14. Testing Turing's theory of morphogenesis in chemical cells.

    PubMed

    Tompkins, Nathan; Li, Ning; Girabawe, Camille; Heymann, Michael; Ermentrout, G Bard; Epstein, Irving R; Fraden, Seth

    2014-03-25

    Alan Turing, in "The Chemical Basis of Morphogenesis" [Turing AM (1952) Philos Trans R Soc Lond 237(641):37-72], described how, in circular arrays of identical biological cells, diffusion can interact with chemical reactions to generate up to six periodic spatiotemporal chemical structures. Turing proposed that one of these structures, a stationary pattern with a chemically determined wavelength, is responsible for differentiation. We quantitatively test Turing's ideas in a cellular chemical system consisting of an emulsion of aqueous droplets containing the Belousov-Zhabotinsky oscillatory chemical reactants, dispersed in oil, and demonstrate that reaction-diffusion processes lead to chemical differentiation, which drives physical morphogenesis in chemical cells. We observe five of the six structures predicted by Turing. In 2D hexagonal arrays, a seventh structure emerges, incompatible with Turing's original model, which we explain by modifying the theory to include heterogeneity. PMID:24616508

  15. CLAUSA restricts tomato leaf morphogenesis and GOBLET expression.

    PubMed

    Bar, Maya; Ben-Herzel, Ori; Kohay, Hagay; Shtein, Ilana; Ori, Naomi

    2015-09-01

    Leaf morphogenesis and differentiation are highly flexible processes. The development of compound leaves is characterized by an extended morphogenesis stage compared with that of simple leaves. The tomato mutant clausa (clau) possesses extremely elaborate compound leaves. Here we show that this elaboration is generated by further extension of the morphogenetic window, partly via the activity of ectopic meristems present on clau leaves. Further, we propose that CLAU might negatively affect expression of the NAM/CUC gene GOBLET (GOB), an important modulator of compound-leaf development, as GOB expression is elevated in clau mutants and reducing GOB expression suppresses the clau phenotype. Expression of GOB is also elevated in the compound leaf mutant lyrate (lyr), and the remarkable enhancement of the clau phenotype by lyr suggests that clau and lyr affect leaf development and GOB in different pathways.

  16. A mirror-symmetric cell division that orchestrates neuroepithelial morphogenesis.

    PubMed

    Tawk, Marcel; Araya, Claudio; Lyons, Dave A; Reugels, Alexander M; Girdler, Gemma C; Bayley, Philippa R; Hyde, David R; Tada, Masazumi; Clarke, Jonathan D W

    2007-04-12

    The development of cell polarity is an essential prerequisite for tissue morphogenesis during embryogenesis, particularly in the development of epithelia. In addition, oriented cell division can have a powerful influence on tissue morphogenesis. Here we identify a novel mode of polarized cell division that generates pairs of neural progenitors with mirror-symmetric polarity in the developing zebrafish neural tube and has dramatic consequences for the organization of embryonic tissue. We show that during neural rod formation the polarity protein Pard3 is localized to the cleavage furrow of dividing progenitors, and then mirror-symmetrically inherited by the two daughter cells. This allows the daughter cells to integrate into opposite sides of the developing neural tube. Furthermore, these mirror-symmetric divisions have powerful morphogenetic influence: when forced to occur in ectopic locations during neurulation, they orchestrate the development of mirror-image pattern formation and the consequent generation of ectopic neural tubes.

  17. Pkd1 regulates lymphatic vascular morphogenesis during development.

    PubMed

    Coxam, Baptiste; Sabine, Amélie; Bower, Neil I; Smith, Kelly A; Pichol-Thievend, Cathy; Skoczylas, Renae; Astin, Jonathan W; Frampton, Emmanuelle; Jaquet, Muriel; Crosier, Philip S; Parton, Robert G; Harvey, Natasha L; Petrova, Tatiana V; Schulte-Merker, Stefan; Francois, Mathias; Hogan, Benjamin M

    2014-05-01

    Lymphatic vessels arise during development through sprouting of precursor cells from veins, which is regulated by known signaling and transcriptional mechanisms. The ongoing elaboration of vessels to form a network is less well understood. This involves cell polarization, coordinated migration, adhesion, mixing, regression, and shape rearrangements. We identified a zebrafish mutant, lymphatic and cardiac defects 1 (lyc1), with reduced lymphatic vessel development. A mutation in polycystic kidney disease 1a was responsible for the phenotype. PKD1 is the most frequently mutated gene in autosomal dominant polycystic kidney disease (ADPKD). Initial lymphatic precursor sprouting is normal in lyc1 mutants, but ongoing migration fails. Loss of Pkd1 in mice has no effect on precursor sprouting but leads to failed morphogenesis of the subcutaneous lymphatic network. Individual lymphatic endothelial cells display defective polarity, elongation, and adherens junctions. This work identifies a highly selective and unexpected role for Pkd1 in lymphatic vessel morphogenesis during development.

  18. Three-dimensional epithelial morphogenesis in the developing Drosophila egg

    PubMed Central

    Osterfield, Miriam; Du, XinXin; Schüpbach, Trudi; Wieschaus, Eric; Shvartsman, Stanislav Y.

    2013-01-01

    Morphogenesis of the respiratory appendages on eggshells of Drosophila species provides a powerful experimental system for studying how cell sheets give rise to complex three-dimensional structures. In Drosophila melanogaster, each of the two tubular eggshell appendages is derived from a primordium comprising two distinct cell types. Using live imaging and three-dimensional image reconstruction, we demonstrate that the transformation of this two-dimensional primordium into a tube involves out-of-plane bending followed by a sequence of spatially ordered cell intercalations. These morphological transformations correlate with the appearance of complementary distributions of myosin and Bazooka in the primordium. These distributions suggest that a two-dimensional pattern of line tensions along cell-cell edges on the apical side of the epithelium is sufficient to produce the observed changes in morphology. Computational modeling shows that this mechanism could explain the main features of tissue deformation and cell rearrangements observed during three-dimensional morphogenesis. PMID:23449472

  19. The buccohypophyseal canal is an ancestral vertebrate trait maintained by modulation in sonic hedgehog signaling

    PubMed Central

    2013-01-01

    Background The pituitary gland is formed by the juxtaposition of two tissues: neuroectoderm arising from the basal diencephalon, and oral epithelium, which invaginates towards the central nervous system from the roof of the mouth. The oral invagination that reaches the brain from the mouth is referred to as Rathke’s pouch, with the tip forming the adenohypophysis and the stalk disappearing after the earliest stages of development. In tetrapods, formation of the cranial base establishes a definitive barrier between the pituitary and oral cavity; however, numerous extinct and extant vertebrate species retain an open buccohypophyseal canal in adulthood, a vestige of the stalk of Rathke’s pouch. Little is currently known about the formation and function of this structure. Here we have investigated molecular mechanisms driving the formation of the buccohypophyseal canal and their evolutionary significance. Results We show that Rathke’s pouch is located at a boundary region delineated by endoderm, neural crest-derived oral mesenchyme and the anterior limit of the notochord, using CD1, R26R-Sox17-Cre and R26R-Wnt1-Cre mouse lines. As revealed by synchrotron X-ray microtomography after iodine staining in mouse embryos, the pouch has a lobulated three-dimensional structure that embraces the descending diencephalon during pituitary formation. Polarisfl/fl; Wnt1-Cre, Ofd1-/- and Kif3a-/- primary cilia mouse mutants have abnormal sonic hedgehog (Shh) signaling and all present with malformations of the anterior pituitary gland and midline structures of the anterior cranial base. Changes in the expressions of Shh downstream genes are confirmed in Gas1-/- mice. From an evolutionary perspective, persistence of the buccohypophyseal canal is a basal character for all vertebrates and its maintenance in several groups is related to a specific morphology of the midline that can be related to modulation in Shh signaling. Conclusion These results provide insight into a poorly

  20. Oscarella lobularis (Homoscleromorpha, Porifera) Regeneration: Epithelial Morphogenesis and Metaplasia.

    PubMed

    Ereskovsky, Alexander V; Borisenko, Ilya E; Lapébie, Pascal; Gazave, Eve; Tokina, Daria B; Borchiellini, Carole

    2015-01-01

    Sponges are known to possess remarkable reconstitutive and regenerative abilities ranging from common wounding or body part regeneration to more impressive re-building of a functional body from dissociated cells. Among the four sponge classes, Homoscleromorpha is notably the only sponge group to possess morphologically distinct basement membrane and specialized cell-junctions, and is therefore considered to possess true epithelia. The consequence of this peculiar organization is the predominance of epithelial morphogenesis during ontogenesis of these sponges. In this work we reveal the underlying cellular mechanisms used during morphogenesis accompanying ectosome regeneration in the homoscleromorph sponge model: Oscarella lobularis. We identified three main sources of novel exopinacoderm during the processes of its regeneration and the restoration of functional peripheral parts of the aquiferous system in O. lobularis: (1) intact exopinacoderm surrounding the wound surface, (2) the endopinacoderm from peripheral exhalant and inhalant canals, and (3) the intact choanoderm found on the wound surface. The basic morphogenetic processes during regeneration are the spreading and fusion of epithelial sheets that merge into one continuous epithelium. Transdifferentiation of choanocytes into exopinacocytes is also present. Epithelial-mesenchymal transition is absent during regeneration. Moreover, we cannot reveal any other morphologically distinct pluripotent cells. In Oscarella, neither blastema formation nor local dedifferentiation and proliferation have been detected, which is probably due to the high morphogenetic plasticity of the tissue. Regeneration in O. lobularis goes through cell transdifferentiation and through the processes, when lost body parts are replaced by the remodeling of the remaining tissue. Morphogenesis during ectosome regeneration in O. lobularis is correlated with its true epithelial organization. Knowledge of the morphological basis of

  1. Oscarella lobularis (Homoscleromorpha, Porifera) Regeneration: Epithelial Morphogenesis and Metaplasia

    PubMed Central

    Ereskovsky, Alexander V.; Borisenko, Ilya E.; Lapébie, Pascal; Gazave, Eve; Tokina, Daria B.; Borchiellini, Carole

    2015-01-01

    Sponges are known to possess remarkable reconstitutive and regenerative abilities ranging from common wounding or body part regeneration to more impressive re-building of a functional body from dissociated cells. Among the four sponge classes, Homoscleromorpha is notably the only sponge group to possess morphologically distinct basement membrane and specialized cell-junctions, and is therefore considered to possess true epithelia. The consequence of this peculiar organization is the predominance of epithelial morphogenesis during ontogenesis of these sponges. In this work we reveal the underlying cellular mechanisms used during morphogenesis accompanying ectosome regeneration in the homoscleromorph sponge model: Oscarella lobularis. We identified three main sources of novel exopinacoderm during the processes of its regeneration and the restoration of functional peripheral parts of the aquiferous system in O. lobularis: (1) intact exopinacoderm surrounding the wound surface, (2) the endopinacoderm from peripheral exhalant and inhalant canals, and (3) the intact choanoderm found on the wound surface. The basic morphogenetic processes during regeneration are the spreading and fusion of epithelial sheets that merge into one continuous epithelium. Transdifferentiation of choanocytes into exopinacocytes is also present. Epithelial-mesenchymal transition is absent during regeneration. Moreover, we cannot reveal any other morphologically distinct pluripotent cells. In Oscarella, neither blastema formation nor local dedifferentiation and proliferation have been detected, which is probably due to the high morphogenetic plasticity of the tissue. Regeneration in O. lobularis goes through cell transdifferentiation and through the processes, when lost body parts are replaced by the remodeling of the remaining tissue. Morphogenesis during ectosome regeneration in O. lobularis is correlated with its true epithelial organization. Knowledge of the morphological basis of

  2. [Genes related with male gonadal morphogenesis in mammals].

    PubMed

    Wu, Jie; Wang, Feng

    2008-04-01

    Gene expressions are sex-specific in the sex development of mammals. Different genes express in different phases and tend to change with the time. The functions of some genes, such as SRY, SOX9, SOX8, DAX1, and FGF9, have already been defined in male gonadal morphogenesis. This paper presents a review of the genes involved in the formation of the male gonad in mammals. PMID:18481432

  3. Testing Turing's Theory of Morphogenesis in Chemical Cells

    NASA Astrophysics Data System (ADS)

    Tompkins, Nathan; Li, Ning; Girabawe, Camille; Heymann, Michael; Ermentrout, G. Bard; Epstein, Irving; Fraden, Seth

    2015-03-01

    Alan Turing's 1952 paper ``The Chemical Basis of Morphogenesis'' described how reaction-diffusion dynamics could create six spatiotemporal patterns including a stationary pattern that could lead to physical morphogenesis (which now bears his name). This stationary ``Turing pattern'' has been observed in continuous media of various chemical systems but never in diffusively coupled discrete reactors as Turing theorized. We have created a system of microfluidically produced chemical compartments containing the Belousov-Zhabotinsky reaction that are designed to fulfill the assumptions of Turing's theoretical system. This system demonstrates all six spatiotemporal patterns that Turing predicted. In particular, we observe the stationary case that bears Turing's name where the cells create a pattern of oxidized and reduced states. As Turing predicted, this chemical heterogeneity gives rise to physical heterogeneity by driving an osmotic flow, swelling the reduced cells and shrinking the oxidized cells. In addition to the six patterns and physical morphogenesis predicted by Turing we observe a seventh pattern of mixed stationary/oscillatory states that is not predicted by Turing. This seventh pattern requires modifying Turing's theory to include slight heterogeneity to match experiments.

  4. Joint shape morphogenesis precedes cavitation of the developing hip joint

    PubMed Central

    Nowlan, Niamh C; Sharpe, James

    2014-01-01

    The biology and mechanobiology of joint cavitation have undergone extensive investigation, but we have almost no understanding of the development of joint shape. Joint morphogenesis, the development of shape, has been identified as the ‘least understood aspect of joint formation’ (2005, Birth Defects Res C Embryo Today 75, 237), despite the clinical relevance of shape morphogenesis to postnatal skeletal malformations such as developmental dysplasia of the hip. In this study, we characterise development of early hip joint shape in the embryonic chick using direct capture 3D imaging. Contrary to formerly held assumptions that cavitation precedes morphogenesis in joint development, we have found that the major anatomical features of the adult hip are present at Hamburger Hamilton (HH)32, a full day prior to cavitation of the joint at HH34. We also reveal that the pelvis undergoes significant changes in orientation with respect to the femur, despite the lack of a joint cavity between the rudiments. Furthermore, we have identified the appearance of the ischium and pubis several developmental stages earlier than was previously reported, illustrating the value and importance of direct capture 3D imaging. PMID:24266523

  5. Embryo mechanics: balancing force production with elastic resistance during morphogenesis.

    PubMed

    Davidson, Lance A

    2011-01-01

    Morphogenesis requires the spatial and temporal control of embryo mechanics, including force production and mechanical resistance to those forces, to coordinate tissue deformation and large-scale movements. Thus, biomechanical processes play a key role in directly shaping the embryo. Additional roles for embryo mechanics during development may include the patterning of positional information and to provide feedback to ensure the success of morphogenetic movements in shaping the larval body and organs. To understand the multiple roles of mechanics during development requires familiarity with engineering principles of the mechanics of structures, the viscoelastic properties of biomaterials, and the integration of force and stress within embryonic structures as morphogenesis progresses. In this chapter, we review the basic engineering principles of biomechanics as they relate to morphogenesis, introduce methods for quantifying embryo mechanics and the limitations of these methods, and outline a formalism for investigating the role of embryo mechanics in birth defects. We encourage the nascent field of embryo mechanics to adopt standard engineering terms and test methods so that studies of diverse organisms can be compared and universal biomechanical principles can be revealed.

  6. Kinetic and Mechanical Analysis of Live Tube Morphogenesis

    PubMed Central

    Cheshire, Alan M.; Kerman, Bilal E.; Zipfel, Warren R.; Spector, Alexander A.; Andrew, Deborah J.

    2008-01-01

    Ribbon is a nuclear BTB-domain protein required for morphogenesis of the salivary gland and trachea. We recently showed that ribbon mutants exhibit decreased Crumbs and Rab11-coincident apical vesicles and increased apical Moesin activity and microvillar structure during tube elongation. To learn how these molecular and morphological changes affect the dynamics of tubulogenesis, we optimized an advanced two-photon microscope to enable high-resolution live imaging of the salivary gland and trachea. Live imaging revealed that ribbon mutant tissues exhibit slowed and incomplete lumenal morphogenesis, consistent with previously described apical defects. Since Moesin activity correlates with cortical stiffness, we hypothesize that ribbon mutants suffer from increased apical stiffness during morphogenesis. We develop this hypothesis through mechanical analysis, using the advantages of live imaging to construct computational elastic and analytical viscoelastic models of tube elongation, which suggest that ribbon mutant tubes exhibit three- to five-fold increased apical stiffness and two-fold increased effective apical viscosity. PMID:18816822

  7. Cardiolipin synthase is required for Streptomyces coelicolor morphogenesis

    PubMed Central

    Jyothikumar, Vinod; Klanbut, Khanungkan; Tiong, John; Roxburgh, James S.; Hunter, Iain S.; Smith, Terry K.; Herron, Paul R.

    2013-01-01

    Summary The fluid mosaic model has recently been amended to account for the existence of membrane domains enriched in certain phospholipids. In rod-shaped bacteria, the anionic phospholipid cardiolipin is enriched at the cell poles but its role in the morphogenesis of the filamentous bacterium Streptomyces coelicolor is unknown. It was impossible to delete clsA (cardiolipin synthase; SCO1389) unless complemented by a second copy of clsA elsewhere in the chromosome. When placed under the control of an inducible promoter, clsA expression, phospholipid profile and morphogenesis became inducer dependent. TLC analysis of phospholipid showed altered profiles upon depletion of clsA expression. Analysis of cardiolipin by mass spectrometry showed two distinct cardiolipin envelopes that reflected differences in acyl chain length; the level of the larger cardiolipin envelope was reduced in concert with clsA expression. ClsA-EGFP did not localize to specific locations, but cardiolipin itself showed enrichment at hyphal tips, branch points and anucleate regions. Quantitative analysis of hyphal dimensions showed that the mycelial architecture and the erection of aerial hyphae were affected by the expression of clsA. Overexpression of clsA resulted in weakened hyphal tips, misshaped aerial hyphae and anucleate spores and demonstrates that cardiolipin synthesis is a requirement for morphogenesis in Streptomyces. PMID:22409773

  8. Gene Expression During Drosophila Wing Morphogenesis and Differentiation

    PubMed Central

    Ren, Nan; Zhu, Chunming; Lee, Haeryun; Adler, Paul N.

    2005-01-01

    The simple cellular composition and array of distally pointing hairs has made the Drosophila wing a favored system for studying planar polarity and the coordination of cellular and tissue level morphogenesis. We carried out a gene expression screen to identify candidate genes that functioned in wing and wing hair morphogenesis. Pupal wing RNA was isolated from tissue prior to, during, and after hair growth and used to probe Affymetrix Drosophila gene chips. We identified 435 genes whose expression changed at least fivefold during this period and 1335 whose expression changed at least twofold. As a functional validation we chose 10 genes where genetic reagents existed but where there was little or no evidence for a wing phenotype. New phenotypes were found for 9 of these genes, providing functional validation for the collection of identified genes. Among the phenotypes seen were a delay in hair initiation, defects in hair maturation, defects in cuticle formation and pigmentation, and abnormal wing hair polarity. The collection of identified genes should be a valuable data set for future studies on hair and bristle morphogenesis, cuticle synthesis, and planar polarity. PMID:15998724

  9. Signaling Involved in Hair Follicle Morphogenesis and Development

    PubMed Central

    Rishikaysh, Pisal; Dev, Kapil; Diaz, Daniel; Qureshi, Wasay Mohiuddin Shaikh; Filip, Stanislav; Mokry, Jaroslav

    2014-01-01

    Hair follicle morphogenesis depends on Wnt, Shh, Notch, BMP and other signaling pathways interplay between epithelial and mesenchymal cells. The Wnt pathway plays an essential role during hair follicle induction, Shh is involved in morphogenesis and late stage differentiation, Notch signaling determines stem cell fate while BMP is involved in cellular differentiation. The Wnt pathway is considered to be the master regulator during hair follicle morphogenesis. Wnt signaling proceeds through EDA/EDAR/NF-κB signaling. NF-κB regulates the Wnt pathway and acts as a signal mediator by upregulating the expression of Shh ligand. Signal crosstalk between epithelial and mesenchymal cells takes place mainly through primary cilia. Primary cilia formation is initiated with epithelial laminin-511 interaction with dermal β-1 integrin, which also upregulates expression of downstream effectors of Shh pathway in dermal lineage. PDGF signal transduction essential for crosstalk is mediated through epithelial PDGF-A and PDGFRα expressed on the primary cilia. Dermal Shh and PDGF signaling up-regulates dermal noggin expression; noggin is a potent inhibitor of BMP signaling which helps in counteracting BMP mediated β-catenin inhibition. This interplay of signaling between the epithelial and dermal lineage helps in epithelial Shh signal amplification. The dermal Wnt pathway helps in upregulation of epithelial Notch expression. Dysregulation of these pathways leads to certain abnormalities and in some cases even tumor outgrowth. PMID:24451143

  10. Evolution of vertebrate colour vision.

    PubMed

    Jacobs, Gerald H; Rowe, Mickey P

    2004-07-01

    Recent years have witnessed a growing interest in learning how colour vision has evolved. This trend has been fuelled by an enhanced understanding of the nature and extent of colour vision among contemporary species, by a deeper understanding of the paleontological record and by the application of new tools from molecular biology. This review provides an assessment of the progress in understanding the evolution of vertebrate colour vision. In so doing, we offer accounts of the evolution of three classes of mechanism important for colour vision--photopigment opsins, oil droplets and retinal organisation--and then examine details of how colour vision has evolved among mammals and, more specifically, among primates.

  11. Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

    NASA Astrophysics Data System (ADS)

    Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

    2014-03-01

    Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

  12. Endocrine disruption in aquatic vertebrates.

    PubMed

    Kloas, Werner; Urbatzka, Ralph; Opitz, Robert; Würtz, Sven; Behrends, Thomas; Hermelink, Björn; Hofmann, Frauke; Jagnytsch, Oana; Kroupova, Hana; Lorenz, Claudia; Neumann, Nadja; Pietsch, Constanze; Trubiroha, Achim; Van Ballegooy, Christoph; Wiedemann, Caterina; Lutz, Ilka

    2009-04-01

    Environmental compounds can interfere with endocrine systems of wildlife and humans. The main sink of such substances, called endocrine disrupters (ED), are surface waters. Thus, aquatic vertebrates, such as fish and amphibians, are most endangered. ED can adversely affect reproductive biology and the thyroid system. ED act by (anti)estrogenic and (anti)androgenic modes of action, resulting in abnormal sexual differentiation and impaired reproduction. These effects are mainly driven by direct interferences of ED with sex steroid receptors rather than indirectly by impacting synthesis and bioavailability of sex steroids, which in turn might affect the hypothalamic-pituitary-gonadal axis. Recent findings reveal that, in addition to the human-produced waste of ED, natural sources, such as parasites and decomposition of leaves, also might act as ED, markedly affecting sexual differentiation and reproduction in fish and amphibians. Although the thyroid system has essential functions in both fish and amphibians, amphibian metamorphosis has been introduced as the most sensitive model to detect thyroidal ED; no suitable fish model exists. Whereas ED may act primarily on only one specific endocrine target, all endocrine systems will eventually be deregulated as they are intimately connected to each other. The recent ecotoxicological issue of pharmaceutically active compounds (PhACs) present in the aquatic environment indicates a high potential for further endocrine modes of action on aquatic vertebrates by ED derived from PhACs, such as glucocorticoids, progestins, and beta-agonists.

  13. Canine Notochordal Cell-Secreted Factors Protect Murine and Human Nucleus Pulposus Cells from Apoptosis by Inhibition of Activated Caspase-9 and Caspase-3/7

    PubMed Central

    Mehrkens, Arne; Karim, M. Zia; Kim, Sarah; Hilario, Raychel; Fehlings, Michael G.; Erwin, William Mark

    2013-01-01

    Introduction Effective therapies that may stop or even reverse disc degeneration remain elusive. A minimally invasive method through which nucleus pulposus (NP) cell viability could be achieved would revolutionize the treatment of degenerative disc disease (DDD). With the presented work, we have investigated if nonchondrodystrophic (NCD) canine intervertebral disc (IVD)-derived notochordal cell conditioned medium (NCCM) and chondrodystrophic (CD) canine IVD-derived conditioned medium (CDCM) are able to protect murine and human NP cells from apoptosis. Materials and Methods We developed NCCM and CDCM from hypoxic culture of freshly isolated NPs from NCD and CD canines, respectively. We obtained murine NP cells from nine different C57BL/6 mice and human NP cells from four patients who underwent surgery for discectomy. The cells were cultured with ADMEM/F-12 (control media), NCCM, or CDCM under hypoxic conditions (3.5% O2) and treated with IL-1β + FasL or Etoposide. All media were supplemented with 2% fetal bovine serum. We then determined the expression of specific apoptotic pathways in the murine and human NP cells by recording activated caspase-8, caspase-9, and caspase-3/7 activity. Results In the murine NP cells, NCCM inhibits IL-1β + FasL- and Etoposide-mediated apoptosis via suppression of activated caspase-9 and caspase-3/7, CDCM demonstrated an inhibitory effect on IL-1β + FasL-mediated apoptosis via caspase-3/7 (Fig. 1A). In the human NP cells, NCCM inhibits Etoposide- mediated apoptosis via suppression of activated caspase-8, caspase-9, and mainly caspase-3/7. CDCM demonstrated an inhibitory effect on Etoposide-mediated apoptosis via suppression of activated caspase-8, caspase-9, and mainly caspase-3/7, though not as effective as NCCM (Fig. 1B). Conclusion IL-1β + FasL are known key molecules in the progression of DDD. Here, we demonstrate that soluble factors secreted by the NCD IVD NP strongly protect murine NP cells not only

  14. Ghrelin Receptors in Non-Mammalian Vertebrates

    PubMed Central

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2012-01-01

    The growth hormone secretagogue-receptor (GHS-R) was discovered in humans and pigs in 1996. The endogenous ligand, ghrelin, was discovered 3 years later, in 1999, and our understanding of the physiological significance of the ghrelin system in vertebrates has grown steadily since then. Although the ghrelin system in non-mammalian vertebrates is a subject of great interest, protein sequence data for the receptor in non-mammalian vertebrates has been limited until recently, and related biological information has not been well organized. In this review, we summarize current information related to the ghrelin receptor in non-mammalian vertebrates. PMID:23882259

  15. No tail co-operates with non-canonical Wnt signaling to regulate posterior body morphogenesis in zebrafish

    PubMed Central

    Marlow, Florence; Gonzalez, Encina M.; Yin, Chunyue; Rojo, Concepcion; Solnica-Krezel, Lilianna

    2016-01-01

    Summary The vertebrate posterior body is formed by a combination of the gastrulation movements that shape the head and anterior trunk and posterior specific cell behaviors. Here, we investigated whether genes that regulate cell movements during gastrulation [no tail (ntl)/brachyury, knypek (kny) and pipetail (ppt)/wnt5] interact to regulate posterior body morphogenesis. Both kny;ntl and ppt;ntl double mutant embryos exhibit synergistic trunk and tail shortening by early segmentation. Gene expression analysis in the compound mutants indicates that anteroposterior germ-layer patterning is largely normal and that the tail elongation defects are not due to failure to specify or maintain posterior tissues. Moreover, ntl interacts with ppt and kny to synergistically regulate the posterior expression of the gene encoding bone morphogenetic protein 4 (bmp4) but not of other known T-box genes, fibroblast growth factor genes or caudal genes. Examination of mitotic and apoptotic cells indicates that impaired tail elongation is not simply due to decreased cell proliferation or increased cell death. Cell tracing in ppt;ntl and kny;ntl mutants demonstrates that the ventral derived posterior tailbud progenitors move into the tailbud. However, gastrulation-like convergence and extension movements and cell movements within the posterior tailbud are impaired. Furthermore, subduction movements of cells into the mesendoderm are reduced in kny;ntl and ppt;ntl mutants. We propose that Ntl and the non-canonical Wnt pathway components Ppt and Kny function in parallel, partially redundant pathways to regulate posterior body development. Our work initiates the genetic dissection of posterior body morphogenesis and links genes to specific tail-forming movements. Moreover, we provide genetic evidence for the notion that tail development entails a continuation of mechanisms regulating gastrulation together with mechanisms unique to the posterior body. PMID:14660439

  16. Hedgehog signaling is required for cranial neural crest morphogenesis and chondrogenesis at the midline in the zebrafish skull.

    PubMed

    Wada, Naoyuki; Javidan, Yashar; Nelson, Sarah; Carney, Thomas J; Kelsh, Robert N; Schilling, Thomas F

    2005-09-01

    Neural crest cells that form the vertebrate head skeleton migrate and interact with surrounding tissues to shape the skull, and defects in these processes underlie many human craniofacial syndromes. Signals at the midline play a crucial role in the development of the anterior neurocranium, which forms the ventral braincase and palate, and here we explore the role of Hedgehog (Hh) signaling in this process. Using sox10:egfp transgenics to follow neural crest cell movements in the living embryo, and vital dye labeling to generate a fate map, we show that distinct populations of neural crest form the two main cartilage elements of the larval anterior neurocranium: the paired trabeculae and the midline ethmoid. By analyzing zebrafish mutants that disrupt sonic hedgehog (shh) expression, we demonstrate that shh is required to specify the movements of progenitors of these elements at the midline, and to induce them to form cartilage. Treatments with cyclopamine, to block Hh signaling at different stages, suggest that although requirements in morphogenesis occur during neural crest migration beneath the brain, requirements in chondrogenesis occur later, as cells form separate trabecular and ethmoid condensations. Cell transplantations indicate that these also reflect different sources of Shh, one from the ventral neural tube that controls trabecular morphogenesis and one from the oral ectoderm that promotes chondrogenesis. Our results suggest a novel role for Shh in the movements of neural crest cells at the midline, as well as in their differentiation into cartilage, and help to explain why both skeletal fusions and palatal clefting are associated with the loss of Hh signaling in holoprosencephalic humans.

  17. No tail co-operates with non-canonical Wnt signaling to regulate posterior body morphogenesis in zebrafish.

    PubMed

    Marlow, Florence; Gonzalez, Encina M; Yin, Chunyue; Rojo, Concepcion; Solnica-Krezel, Lilianna

    2004-01-01

    The vertebrate posterior body is formed by a combination of the gastrulation movements that shape the head and anterior trunk and posterior specific cell behaviors. Here, we investigated whether genes that regulate cell movements during gastrulation [no tail (ntl)/brachyury, knypek (kny) and pipetail (ppt)/wnt5] interact to regulate posterior body morphogenesis. Both kny;ntl and ppt;ntl double mutant embryos exhibit synergistic trunk and tail shortening by early segmentation. Gene expression analysis in the compound mutants indicates that anteroposterior germ-layer patterning is largely normal and that the tail elongation defects are not due to failure to specify or maintain posterior tissues. Moreover, ntl interacts with ppt and kny to synergistically regulate the posterior expression of the gene encoding bone morphogenetic protein 4 (bmp4) but not of other known T-box genes, fibroblast growth factor genes or caudal genes. Examination of mitotic and apoptotic cells indicates that impaired tail elongation is not simply due to decreased cell proliferation or increased cell death. Cell tracing in ppt;ntl and kny;ntl mutants demonstrates that the ventral derived posterior tailbud progenitors move into the tailbud. However, gastrulation-like convergence and extension movements and cell movements within the posterior tailbud are impaired. Furthermore, subduction movements of cells into the mesendoderm are reduced in kny;ntl and ppt;ntl mutants. We propose that Ntl and the non-canonical Wnt pathway components Ppt and Kny function in parallel, partially redundant pathways to regulate posterior body development. Our work initiates the genetic dissection of posterior body morphogenesis and links genes to specific tail-forming movements. Moreover, we provide genetic evidence for the notion that tail development entails a continuation of mechanisms regulating gastrulation together with mechanisms unique to the posterior body.

  18. Characterization and developmental expression of the amphioxus homolog of Notch (AmphiNotch): evolutionary conservation of multiple expression domains in amphioxus and vertebrates.

    PubMed

    Holland, L Z; Rached, L A; Tamme, R; Holland, N D; Kortschak, D; Inoko, H; Shiina, T; Burgtorf, C; Lardelli, M

    2001-04-15

    Notch encodes a transmembrane protein that functions in intercellular signaling. Although there is one Notch gene in Drosophila, vertebrates have three or more with overlapping patterns of embryonic expression. We cloned the entire 7575-bp coding region of an amphioxus Notch gene (AmphiNotch), encoding 2524 amino acids, and obtained the exon/intron organization from a genomic cosmid clone. Southern blot and PCR data indicate that AmphiNotch is the only Notch gene in amphioxus. AmphiNotch, like Drosophila Notch and vertebrate Notch1 and Notch2, has 36 EGF repeats, 3 Notch/lin-12 repeats, a transmembrane region, and 6 ankyrin repeats. Phylogenetic analysis places it at the base of all the vertebrate genes, suggesting it is similar to the ancestral gene from which the vertebrate Notch family genes evolved. AmphiNotch is expressed in all three embryonic germ layers in spatiotemporal patterns strikingly similar to those of all the vertebrate homologs combined. In the developing nerve cord, AmphiNotch is first expressed in the posteriormost part of the neural plate, then it becomes more broadly expressed and later is localized dorsally in the anteriormost part of the nerve cord corresponding to the diencephalon. In late embryos and larvae, AmphiNotch is also expressed in parts of the pharyngeal endoderm, in the anterior gut diverticulum, and, like AmphiPax2/5/8, in the rudiment of Hatschek's kidney. A comparison with Notch1 and Pax5 and Pax8 expression in the embryonic mouse kidney helps support homology of the amphioxus and vertebrate kidneys. AmphiNotch is also an early marker for presumptive mesoderm, transcripts first being detectable at the gastrula stage in a ring of mesendoderm just inside the blastopore and subsequently in the posterior mesoderm, notochord, and somites. As in sea urchins and vertebrates, these domains of AmphiNotch expression overlap with those of several Wnt genes and brachyury. These relationships suggest that amphioxus shares with other

  19. Developmental evolutionary biology of the vertebrate ear: conserving mechanoelectric transduction and developmental pathways in diverging morphologies

    NASA Technical Reports Server (NTRS)

    Fritzsch, B.; Beisel, K. W.; Bermingham, N. A.

    2000-01-01

    This brief overview shows that a start has been made to molecularly dissect vertebrate ear development and its evolutionary conservation to the development of the insect hearing organ. However, neither the patterning process of the ear nor the patterning process of insect sensory organs is sufficiently known at the moment to provide more than a first glimpse. Moreover, hardly anything is known about otocyst development of the cephalopod molluscs, another triploblast lineage that evolved complex 'ears'. We hope that the apparent conserved functional and cellular components present in the ciliated sensory neurons/hair cells will also be found in the genes required for vertebrate ear and insect sensory organ morphogenesis (Fig. 3). Likewise, we expect that homologous pre-patterning genes will soon be identified for the non-sensory cell development, which is more than a blocking of neuronal development through the Delta/Notch signaling system. Generation of the apparently unique ear could thus represent a multiplication of non-sensory cells by asymmetric and symmetric divisions as well as modification of existing patterning process by implementing novel developmental modules. In the final analysis, the vertebrate ear may come about by increasing the level of gene interactions in an already existing and highly conserved interactive cascade of bHLH genes. Since this was apparently achieved in all three lineages of triploblasts independently (Fig. 3), we now need to understand how much of the morphogenetic cascades are equally conserved across phyla to generate complex ears. The existing mutations in humans and mice may be able to point the direction of future research to understand the development of specific cell types and morphologies in the formation of complex arthropod, cephalopod, and vertebrate 'ears'.

  20. Third-generation percutaneous vertebral augmentation systems.

    PubMed

    Vanni, Daniele; Galzio, Renato; Kazakova, Anna; Pantalone, Andrea; Grillea, Giovanni; Bartolo, Marcello; Salini, Vincenzo; Magliani, Vincenzo

    2016-03-01

    Currently, there is no general consensus about the management of osteoporotic vertebral fractures (OVF). In the past, conservative treatment for at least one month was deemed appropriate for the majority of vertebral fractures. When pain persisted after conservative treatment, it was necessary to consider surgical interventions including: vertebroplasty for vertebral fractures with less than 30% loss of height of the affected vertebral body and kyphoplasty for vertebral fractures with greater than 30% loss of height. Currently, this type of treatment is not feasible. Herein we review the characteristics and methods of operation of three of the most common percutaneous vertebral augmentation systems (PVAS) for the treatment of OVF: Vertebral Body Stenting(®) (VBS), OsseoFix(®) and Spine Jack(®). VBS is a titanium device accompanied by a hydraulic (as opposed to mechanical) working system which allows a partial and not immediate possibility to control the opening of the device. On the other hand, OsseoFix(®) and Spine Jack(®) are accompanied by a mechanical working system which allows a progressive and controlled reduction of the vertebral fracture. Another important aspect to consider is the vertebral body height recovery. OsseoFix(®) has an indirect mechanism of action: the compaction of the trabecular bone causes an increase in the vertebral body height. Unlike the Vertebral Body Stenting(®) and Spine Jack(®), the OsseoFix(®) has no direct lift mechanism. Therefore, for these characteristics and for the force that this device is able to provide. In our opinion, Spine Jack(®) is the only device also suitable for the treatment OVF, traumatic fracture (recent, old or inveterate) and primary or secondary bone tumors. PMID:27683690

  1. Third-generation percutaneous vertebral augmentation systems

    PubMed Central

    Galzio, Renato; Kazakova, Anna; Pantalone, Andrea; Grillea, Giovanni; Bartolo, Marcello; Salini, Vincenzo; Magliani, Vincenzo

    2016-01-01

    Currently, there is no general consensus about the management of osteoporotic vertebral fractures (OVF). In the past, conservative treatment for at least one month was deemed appropriate for the majority of vertebral fractures. When pain persisted after conservative treatment, it was necessary to consider surgical interventions including: vertebroplasty for vertebral fractures with less than 30% loss of height of the affected vertebral body and kyphoplasty for vertebral fractures with greater than 30% loss of height. Currently, this type of treatment is not feasible. Herein we review the characteristics and methods of operation of three of the most common percutaneous vertebral augmentation systems (PVAS) for the treatment of OVF: Vertebral Body Stenting® (VBS), OsseoFix® and Spine Jack®. VBS is a titanium device accompanied by a hydraulic (as opposed to mechanical) working system which allows a partial and not immediate possibility to control the opening of the device. On the other hand, OsseoFix® and Spine Jack® are accompanied by a mechanical working system which allows a progressive and controlled reduction of the vertebral fracture. Another important aspect to consider is the vertebral body height recovery. OsseoFix® has an indirect mechanism of action: the compaction of the trabecular bone causes an increase in the vertebral body height. Unlike the Vertebral Body Stenting® and Spine Jack®, the OsseoFix® has no direct lift mechanism. Therefore, for these characteristics and for the force that this device is able to provide. In our opinion, Spine Jack® is the only device also suitable for the treatment OVF, traumatic fracture (recent, old or inveterate) and primary or secondary bone tumors.

  2. Third-generation percutaneous vertebral augmentation systems

    PubMed Central

    Galzio, Renato; Kazakova, Anna; Pantalone, Andrea; Grillea, Giovanni; Bartolo, Marcello; Salini, Vincenzo; Magliani, Vincenzo

    2016-01-01

    Currently, there is no general consensus about the management of osteoporotic vertebral fractures (OVF). In the past, conservative treatment for at least one month was deemed appropriate for the majority of vertebral fractures. When pain persisted after conservative treatment, it was necessary to consider surgical interventions including: vertebroplasty for vertebral fractures with less than 30% loss of height of the affected vertebral body and kyphoplasty for vertebral fractures with greater than 30% loss of height. Currently, this type of treatment is not feasible. Herein we review the characteristics and methods of operation of three of the most common percutaneous vertebral augmentation systems (PVAS) for the treatment of OVF: Vertebral Body Stenting® (VBS), OsseoFix® and Spine Jack®. VBS is a titanium device accompanied by a hydraulic (as opposed to mechanical) working system which allows a partial and not immediate possibility to control the opening of the device. On the other hand, OsseoFix® and Spine Jack® are accompanied by a mechanical working system which allows a progressive and controlled reduction of the vertebral fracture. Another important aspect to consider is the vertebral body height recovery. OsseoFix® has an indirect mechanism of action: the compaction of the trabecular bone causes an increase in the vertebral body height. Unlike the Vertebral Body Stenting® and Spine Jack®, the OsseoFix® has no direct lift mechanism. Therefore, for these characteristics and for the force that this device is able to provide. In our opinion, Spine Jack® is the only device also suitable for the treatment OVF, traumatic fracture (recent, old or inveterate) and primary or secondary bone tumors. PMID:27683690

  3. Origin of the vertebrate body plan via mechanically biased conservation of regular geometrical patterns in the structure of the blastula.

    PubMed

    Edelman, David B; McMenamin, Mark; Sheesley, Peter; Pivar, Stuart

    2016-09-01

    We present a plausible account of the origin of the archetypal vertebrate bauplan. We offer a theoretical reconstruction of the geometrically regular structure of the blastula resulting from the sequential subdivision of the egg, followed by mechanical deformations of the blastula in subsequent stages of gastrulation. We suggest that the formation of the vertebrate bauplan during development, as well as fixation of its variants over the course of evolution, have been constrained and guided by global mechanical biases. Arguably, the role of such biases in directing morphology-though all but neglected in previous accounts of both development and macroevolution-is critical to any substantive explanation for the origin of the archetypal vertebrate bauplan. We surmise that the blastula inherently preserves the underlying geometry of the cuboidal array of eight cells produced by the first three cleavages that ultimately define the medial-lateral, dorsal-ventral, and anterior-posterior axes of the future body plan. Through graphical depictions, we demonstrate the formation of principal structures of the vertebrate body via mechanical deformation of predictable geometrical patterns during gastrulation. The descriptive rigor of our model is supported through comparisons with previous characterizations of the embryonic and adult vertebrate bauplane. Though speculative, the model addresses the poignant absence in the literature of any plausible account of the origin of vertebrate morphology. A robust solution to the problem of morphogenesis-currently an elusive goal-will only emerge from consideration of both top-down (e.g., the mechanical constraints and geometric properties considered here) and bottom-up (e.g., molecular and mechano-chemical) influences. PMID:27392530

  4. Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis.

    PubMed

    Chai, Y; Jiang, X; Ito, Y; Bringas, P; Han, J; Rowitch, D H; Soriano, P; McMahon, A P; Sucov, H M

    2000-04-01

    Neural crest cells are multipotential stem cells that contribute extensively to vertebrate development and give rise to various cell and tissue types. Determination of the fate of mammalian neural crest has been inhibited by the lack of appropriate markers. Here, we make use of a two-component genetic system for indelibly marking the progeny of the cranial neural crest during tooth and mandible development. In the first mouse line, Cre recombinase is expressed under the control of the Wnt1 promoter as a transgene. Significantly, Wnt1 transgene expression is limited to the migrating neural crest cells that are derived from the dorsal CNS. The second mouse line, the ROSA26 conditional reporter (R26R), serves as a substrate for the Cre-mediated recombination. Using this two-component genetic system, we have systematically followed the migration and differentiation of the cranial neural crest (CNC) cells from E9.5 to 6 weeks after birth. Our results demonstrate, for the first time, that CNC cells contribute to the formation of condensed dental mesenchyme, dental papilla, odontoblasts, dentine matrix, pulp, cementum, periodontal ligaments, chondrocytes in Meckel's cartilage, mandible, the articulating disc of temporomandibular joint and branchial arch nerve ganglia. More importantly, there is a dynamic distribution of CNC- and non-CNC-derived cells during tooth and mandibular morphogenesis. These results are a first step towards a comprehensive understanding of neural crest cell migration and differentiation during mammalian craniofacial development. Furthermore, this transgenic model also provides a new tool for cell lineage analysis and genetic manipulation of neural-crest-derived components in normal and abnormal embryogenesis. PMID:10725243

  5. Vertebral fracture assessment in acromegaly.

    PubMed

    Madeira, Miguel; Neto, Leonardo Vieira; Torres, Carolina Hammes; de Mendonça, Laura Maria Carvalho; Gadelha, Mônica Roberto; de Farias, Maria Lúcia Fleiuss

    2013-01-01

    Most vertebral fractures (VFs) are asymptomatic and incidentally found on X-rays. The effects of acromegaly on bone mineral density (BMD) are still controversial, and the prevalence of VFs in this specific population remains uncertain. The objective of this study was to assess VFs in acromegaly through vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA). Seventy-five acromegalic patients from the same center (53 female; age: 48.9±14.5yr) were enrolled in this study. None of them referred previous fragility fracture. They were divided according to the presence or absence of moderate or severe VFs on VFA, a densitometric spine imaging. Age, gender, estimated duration of disease, insulin-like growth factor I levels, disease control and gonadal status, as well as BMD and body composition (analyzed by DXA) were compared between these 2 groups. A prevalence of 10.6% of clinically unapparent VFs was observed. Eight patients had 13 moderate or severe VFs, and only one of them had osteoporosis at densitometry. There was a trend to longer duration of acromegaly before diagnosis, higher prevalence of hypogonadism, and higher BMD Z-score at lumbar spine and femoral neck in fractured patients, without reaching statistical significance. There is a significant prevalence of moderate and severe VFs in acromegalic patients, independently of BMD. More longitudinal and controlled studies are needed to recommend the use of VFA in all acromegalic patients submitted to DXA scan. VFA is simple, practical, uses low radiation, and may provide important information in the management of acromegaly.

  6. Idiopathic segmental sclerosis of vertebral bodies

    SciTech Connect

    McCarthy, E.F.; Dorfman, H.D.

    1982-12-01

    Five cases of idiopathic vetebral sclerosis are presented. The features of this condition are segmental vertebral sclerosis of a single lumbar vertebra in a young adult without disc space narrowing or alteration of vertebral contour. The differential diagnosis is discussed. Lumbar vertebra biopsies of three patients showed reactive nonspecific osteosclerosis.

  7. A Chick Embryo in-Vitro Model of Knee Morphogenesis

    PubMed Central

    Rodriguez, Edward K.; Munasinghe, Jeeva

    2016-01-01

    Background: In this feasibility study, a mechanically loaded in-vitro tissue culture model of joint morphogenesis using the isolated lower extremity of the 8 day old chick embryo was developed to assess the effects of mechanical loading on joint morphogenesis. Methods: The developed in-vitro system allows controlled flexion and extension of the chick embryonic knee with a range of motion of 20 degrees from a resting position of 90-100 degrees of flexion. Joint morphogenesis at 2, 3, 4 and 7 days of culture was assessed by histology and micro MRI in 4 specimen types: undisturbed in-ovo control embryos, in-ovo paralyzed embryos, in-vitro unloaded limb cultures, and in-vitro loaded limb cultures. Relative glycosaminoglycan (GAG) concentration across the joint was assessed with an MRI technique referred to as dGEMRIC (delayed gadolinium enhanced MRI of cartilage) where T1 is proportional to glycosaminoglycan concentration. Results: Average T1 over the entire tissue image for the normal control (IC) knee was 480 msec; for the 4 day loaded specimen average T1 was 354 msec; and for the 7 day loaded specimens T1 was 393 msec. The 4 day unloaded specimen had an average T1 of 279 msec while the 7 day unloaded specimen had an average T1 of 224 msec. The higher T1 values in loaded than unloaded specimens suggest that more glycosaminoglycan is produced in the loaded culture than in the unloaded preparation. Conclusion: Isolated limb tissue cultures under flexion-extension load can be viable and exhibit more progression of joint differentiation and glycosaminoglycan production than similarly cultured but unloaded specimens. However, when compared with controls consisting of intact undisturbed embryos in-ovo, the isolated loaded limbs in culture do not demonstrate equivalent amounts of absolute growth or joint differentiation. PMID:27200386

  8. Vitamin D(3) receptor ablation alters mammary gland morphogenesis.

    PubMed

    Zinser, Glendon; Packman, Kathryn; Welsh, JoEllen

    2002-07-01

    Postnatal mammary gland morphogenesis is achieved through coordination of signaling networks in both the epithelial and stromal cells of the developing gland. While the major proliferative hormones driving pubertal mammary gland development are estrogen and progesterone, studies in transgenic and knockout mice have successfully identified other steroid and peptide hormones that impact on mammary gland development. The vitamin D(3) receptor (VDR), whose ligand 1,25-dihydroxyvitamin D(3) is the biologically active form of vitamin D(3), has been implicated in control of differentiation, cell cycle and apoptosis of mammary cells in culture, but little is known about the physiological relevance of the vitamin D(3) endocrine system in the developing gland. In these studies, we report the expression of the VDR in epithelial cells of the terminal end bud and subtending ducts, in stromal cells and in a subset of lymphocytes within the lymph node. In the terminal end bud, a distinct gradient of VDR expression is observed, with weak VDR staining in proliferative populations and strong VDR staining in differentiated populations. The role of the VDR in ductal morphogenesis was examined in Vdr knockout mice fed high dietary Ca(2+) which normalizes fertility, serum estrogen and neonatal growth. Our results indicate that mammary glands from virgin Vdr knockout mice are heavier and exhibit enhanced growth, as evidenced by higher numbers of terminal end buds, greater ductal outgrowth and enhanced secondary branch points, compared with glands from age- and weight-matched wild-type mice. In addition, glands from Vdr knockout mice exhibit enhanced growth in response to exogenous estrogen and progesterone, both in vivo and in organ culture, compared with glands from wild-type mice. Our data provide the first in vivo evidence that 1,25-dihydroxyvitamin D(3) and the VDR impact on ductal elongation and branching morphogenesis during pubertal development of the mammary gland. Collectively

  9. Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis

    PubMed Central

    Simpson, Cory L.; Patel, Dipal M.; Green, Kathleen J.

    2012-01-01

    To provide a stable environmental barrier, the epidermis requires an integrated network of cytoskeletal elements and cellular junctions. Nevertheless, the epidermis ranks among the body’s most dynamic tissues, continually regenerating itself and responding to cutaneous insults. As keratinocytes journey from the basal compartment towards the cornified layers, they completely reorganize their adhesive junctions and cytoskeleton. These architectural components are more than just rivets and scaffolds — they are active participants in epidermal morphogenesis that regulate epidermal polarization, signalling and barrier formation. PMID:21860392

  10. Quantum morphogenesis: a variation on Thom's catastrophe theory.

    PubMed

    Aerts, Diederik; Czachor, Marek; Gabora, Liane; Kuna, Maciej; Posiewnik, Andrzej; Pykacz, Jarosław; Syty, Monika; Aerts, Dirk

    2003-05-01

    Noncommutative propositions are characteristic of both quantum and nonquantum (sociological, biological, and psychological) situations. In a Hilbert space model, states, understood as correlations between all the possible propositions, are represented by density matrices. If systems in question interact via feedback with environment, their dynamics is nonlinear. Nonlinear evolutions of density matrices lead to the phenomenon of morphogenesis that may occur in noncommutative systems. Several explicit exactly solvable models are presented, including "birth and death of an organism" and "development of complementary properties." PMID:12786197

  11. The mechanics of development: models and methods for tissue morphogenesis

    PubMed Central

    Gjorevski, Nikolce; Nelson, Celeste M.

    2011-01-01

    Embryonic development is a physical process during which masses of cells are sculpted into functional organs. The mechanical properties of tissues and the forces exerted on them serve as epigenetic regulators of morphogenesis. Understanding these mechanobiological effects in the embryo requires new experimental approaches. Here we focus on branching of the lung airways and bending of the heart tube to describe examples of mechanical and physical cues that guide cell fate decisions and organogenesis. We highlight recent technological advances to measure tissue elasticity and endogenous mechanical stresses in real time during organ development. We also discuss recent progress in manipulating forces in intact embryos. PMID:20860059

  12. Quantum morphogenesis: A variation on Thom's catastrophe theory

    NASA Astrophysics Data System (ADS)

    Aerts, Dirk; Czachor, Marek; Gabora, Liane; Kuna, Maciej; Posiewnik, Andrzej; Pykacz, Jarosław; Syty, Monika

    2003-05-01

    Noncommutative propositions are characteristic of both quantum and nonquantum (sociological, biological, and psychological) situations. In a Hilbert space model, states, understood as correlations between all the possible propositions, are represented by density matrices. If systems in question interact via feedback with environment, their dynamics is nonlinear. Nonlinear evolutions of density matrices lead to the phenomenon of morphogenesis that may occur in noncommutative systems. Several explicit exactly solvable models are presented, including “birth and death of an organism” and “development of complementary properties.”

  13. Lymphatic vascular morphogenesis in development, physiology, and disease.

    PubMed

    Schulte-Merker, Stefan; Sabine, Amélie; Petrova, Tatiana V

    2011-05-16

    The lymphatic vasculature constitutes a highly specialized part of the vascular system that is essential for the maintenance of interstitial fluid balance, uptake of dietary fat, and immune response. Recently, there has been an increased awareness of the importance of lymphatic vessels in many common pathological conditions, such as tumor cell dissemination and chronic inflammation. Studies of embryonic development and genetically engineered animal models coupled with the discovery of mutations underlying human lymphedema syndromes have contributed to our understanding of mechanisms regulating normal and pathological lymphatic morphogenesis. It is now crucial to use this knowledge for the development of novel therapies for human diseases.

  14. Nanotechnology for treating osteoporotic vertebral fractures

    PubMed Central

    Gao, Chunxia; Wei, Donglei; Yang, Huilin; Chen, Tao; Yang, Lei

    2015-01-01

    Osteoporosis is a serious public health problem affecting hundreds of millions of aged people worldwide, with severe consequences including vertebral fractures that are associated with significant morbidity and mortality. To augment or treat osteoporotic vertebral fractures, a number of surgical approaches including minimally invasive vertebroplasty and kyphoplasty have been developed. However, these approaches face problems and difficulties with efficacy and long-term stability. Recent advances and progress in nanotechnology are opening up new opportunities to improve the surgical procedures for treating osteoporotic vertebral fractures. This article reviews the improvements enabled by new nanomaterials and focuses on new injectable biomaterials like bone cements and surgical instruments for treating vertebral fractures. This article also provides an introduction to osteoporotic vertebral fractures and current clinical treatments, along with the rationale and efficacy of utilizing nanomaterials to modify and improve biomaterials or instruments. In addition, perspectives on future trends with injectable bone cements and surgical instruments enhanced by nanotechnology are provided. PMID:26316746

  15. Lamprey: a model for vertebrate evolutionary research.

    PubMed

    Xu, Yang; Zhu, Si-Wei; Li, Qing-Wei

    2016-09-18

    Lampreys belong to the superclass Cyclostomata and represent the most ancient group of vertebrates. Existing for over 360 million years, they are known as living fossils due to their many evolutionally conserved features. They are not only a keystone species for studying the origin and evolution of vertebrates, but also one of the best models for researching vertebrate embryonic development and organ differentiation. From the perspective of genetic information, the lamprey genome remains primitive compared with that of other higher vertebrates, and possesses abundant functional genes. Through scientific and technological progress, scientists have conducted in-depth studies on the nervous, endocrine, and immune systems of lampreys. Such research has significance for understanding and revealing the origin and evolution of vertebrates, and could contribute to a greater understanding of human diseases and treatments. This review presents the current progress and significance of lamprey research. PMID:27686784

  16. Lamprey: a model for vertebrate evolutionary research

    PubMed Central

    XU, Yang; ZHU, Si-Wei; LI, Qing-Wei

    2016-01-01

    Lampreys belong to the superclass Cyclostomata and represent the most ancient group of vertebrates. Existing for over 360 million years, they are known as living fossils due to their many evolutionally conserved features. They are not only a keystone species for studying the origin and evolution of vertebrates, but also one of the best models for researching vertebrate embryonic development and organ differentiation. From the perspective of genetic information, the lamprey genome remains primitive compared with that of other higher vertebrates, and possesses abundant functional genes. Through scientific and technological progress, scientists have conducted in-depth studies on the nervous, endocrine, and immune systems of lampreys. Such research has significance for understanding and revealing the origin and evolution of vertebrates, and could contribute to a greater understanding of human diseases and treatments. This review presents the current progress and significance of lamprey research. PMID:27686784

  17. Nanotechnology for treating osteoporotic vertebral fractures.

    PubMed

    Gao, Chunxia; Wei, Donglei; Yang, Huilin; Chen, Tao; Yang, Lei

    2015-01-01

    Osteoporosis is a serious public health problem affecting hundreds of millions of aged people worldwide, with severe consequences including vertebral fractures that are associated with significant morbidity and mortality. To augment or treat osteoporotic vertebral fractures, a number of surgical approaches including minimally invasive vertebroplasty and kyphoplasty have been developed. However, these approaches face problems and difficulties with efficacy and long-term stability. Recent advances and progress in nanotechnology are opening up new opportunities to improve the surgical procedures for treating osteoporotic vertebral fractures. This article reviews the improvements enabled by new nanomaterials and focuses on new injectable biomaterials like bone cements and surgical instruments for treating vertebral fractures. This article also provides an introduction to osteoporotic vertebral fractures and current clinical treatments, along with the rationale and efficacy of utilizing nanomaterials to modify and improve biomaterials or instruments. In addition, perspectives on future trends with injectable bone cements and surgical instruments enhanced by nanotechnology are provided. PMID:26316746

  18. Lamprey: a model for vertebrate evolutionary research.

    PubMed

    Xu, Yang; Zhu, Si-Wei; Li, Qing-Wei

    2016-09-18

    Lampreys belong to the superclass Cyclostomata and represent the most ancient group of vertebrates. Existing for over 360 million years, they are known as living fossils due to their many evolutionally conserved features. They are not only a keystone species for studying the origin and evolution of vertebrates, but also one of the best models for researching vertebrate embryonic development and organ differentiation. From the perspective of genetic information, the lamprey genome remains primitive compared with that of other higher vertebrates, and possesses abundant functional genes. Through scientific and technological progress, scientists have conducted in-depth studies on the nervous, endocrine, and immune systems of lampreys. Such research has significance for understanding and revealing the origin and evolution of vertebrates, and could contribute to a greater understanding of human diseases and treatments. This review presents the current progress and significance of lamprey research.

  19. Localization of peripherin/rds in the disk membranes of cone and rod photoreceptors: relationship to disk membrane morphogenesis and retinal degeneration

    PubMed Central

    1992-01-01

    The outer segments of vertebrate rod photoreceptor cells consist of an ordered stack of membrane disks, which, except for a few nascent disks at the base of the outer segment, is surrounded by a separate plasma membrane. Previous studies indicate that the protein, peripherin or peripherin/rds, is localized along the rim of mature disks of rod outer segments. A mutation in the gene for this protein has been reported to be responsible for retinal degeneration in the rds mouse. In the present study, we have shown by immunogold labeling of rat and ground squirrel retinas that peripherin/rds is present in the disk rims of cone outer segments as well as rod outer segments. Additionally, in the basal regions of rod and cone outer segments, where disk morphogenesis occurs, we have found that the distribution of peripherin/rds is restricted to a region that is adjacent to the cilium. Extension of its distribution from the cilium coincides with the formation of the disk rim. These results support the model of disk membrane morphogenesis that predicts rim formation to be a second stage of growth, after the first stage in which the ciliary plasma membrane evaginates to form open nascent disks. The results also indicate how the proteins of the outer segment plasma membrane and the disk membranes are sorted into their separate domains: different sets of proteins may be incorporated into membrane outgrowths during different growth stages of disk morphogenesis. Finally, the presence of peripherin/rds protein in both cone and rod outer segment disks, together with the phenotype of the rds mouse, which is characterized by the failure of both rod and cone outer segment formation, suggest that the same rds gene is expressed in both types of photoreceptor cells. PMID:1730772

  20. The Pea Seedling as a Model of Normal and Abnormal Morphogenesis

    ERIC Educational Resources Information Center

    Kurkdjian, Armen; And Others

    1974-01-01

    Describes several simple and inexpensive experiments designed to facilitate the study of normal and abnormal morphogenesis in the biology laboratory. Seedlings of the common garden pea are used in the experiments, and abnormal morphogenesis (tumors) are induced by a virulent strain of the crown-gall organism, Agrobacterium tumefaciens. (JR)

  1. Physics and the canalization of morphogenesis: a grand challenge in organismal biology

    PubMed Central

    von Dassow, Michelangelo; Davidson, Lance A.

    2011-01-01

    Morphogenesis takes place in a background of organism-to-organism and environmental variation. Therefore, a fundamental question in the study of morphogenesis is how the mechanical processes of tissue movement and deformation are affected by that variability, and in turn, how the mechanics of the system modulates phenotypic variation. We highlight a few key factors, including environmental temperature, embryo size, and environmental chemistry that might perturb the mechanics of morphogenesis in natural populations. Then we discuss several ways in which mechanics – including feedback from mechanical cues – might influence intra-specific variation in morphogenesis. To understand morphogenesis it will be necessary to consider whole-organism, environment, and evolutionary scales because these larger scales present the challenges that developmental mechanisms have evolved to cope with. Studying the variation organisms express and the variation organisms experience will aid in deciphering the causes of birth defects. PMID:21750364

  2. Physics and the canalization of morphogenesis: a grand challenge in organismal biology

    NASA Astrophysics Data System (ADS)

    von Dassow, Michelangelo; Davidson, Lance A.

    2011-08-01

    Morphogenesis takes place against a background of organism-to-organism and environmental variation. Therefore, fundamental questions in the study of morphogenesis include: How are the mechanical processes of tissue movement and deformation affected by that variability, and in turn, how do the mechanic of the system modulate phenotypic variation? We highlight a few key factors, including environmental temperature, embryo size and environmental chemistry that might perturb the mechanics of morphogenesis in natural populations. Then we discuss several ways in which mechanics—including feedback from mechanical cues—might influence intra-specific variation in morphogenesis. To understand morphogenesis it will be necessary to consider whole-organism, environment and evolutionary scales because these larger scales present the challenges that developmental mechanisms have evolved to cope with. Studying the variation organisms express and the variation organisms experience will aid in deciphering the causes of birth defects.

  3. Mitotic chromosome condensation in vertebrates

    SciTech Connect

    Vagnarelli, Paola

    2012-07-15

    Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes of

  4. Evolutionary stasis in pollen morphogenesis due to natural selection.

    PubMed

    Matamoro-Vidal, Alexis; Prieu, Charlotte; Furness, Carol A; Albert, Béatrice; Gouyon, Pierre-Henri

    2016-01-01

    The contribution of developmental constraints and selective forces to the determination of evolutionary patterns is an important and unsolved question. We test whether the long-term evolutionary stasis observed for pollen morphogenesis (microsporogenesis) in eudicots is due to developmental constraints or to selection on a morphological trait shaped by microsporogenesis: the equatorial aperture pattern. Most eudicots have three equatorial apertures but several taxa have independently lost the equatorial pattern and have microsporogenesis decoupled from aperture pattern determination. If selection on the equatorial pattern limits variation, we expect to see increased variation in microsporogenesis in the nonequatorial clades. Variation of microsporogenesis was studied using phylogenetic comparative analyses in 83 species dispersed throughout eudicots including species with and without equatorial apertures. The species that have lost the equatorial pattern have highly variable microsporogenesis at the intra-individual and inter-specific levels regardless of their pollen morphology, whereas microsporogenesis remains stable in species with the equatorial pattern. The observed burst of variation upon loss of equatorial apertures shows that there are no strong developmental constraints precluding variation in microsporogenesis, and that the stasis is likely to be due principally to selective pressure acting on pollen morphogenesis because of its implication in the determination of the equatorial aperture pattern.

  5. YAP overexpression affects tooth morphogenesis and enamel knot patterning.

    PubMed

    Liu, M; Zhao, S; Wang, X P

    2014-05-01

    Teeth develop through distinct morphological stages. At the cap stage, a compactly clustered and concentrically arranged cell mass, the enamel knot, appears at the tip of the enamel organ. Cells in this knot express sets of key molecules, and as such have been proposed to act as a signaling center directing tooth morphogenesis and tooth cusp formation. YAP is a transcriptional co-activator of the Hippo signaling pathway that is essential for the proper regulation of organ growth. In this study, we analyzed the tooth phenotype in transgenic mice that overexpressed a constitutively active form of YAP in the dental epithelium. We found that overexpression of YAP resulted in deformed tooth morphogenesis with widened dental lamina. In addition, the enamel knot was mislocated to the upper portion of the enamel organ, where it remained devoid of proliferating cells and contained apoptotic cells with intense Edar transcripts and reduced E-cadherin expression. Interestingly, some signaling molecules, such as Shh, Fgf4, and Wnt10a, were not expressed in this mislocated enamel knot, but remained at the tip of the enamel organ. Analysis of these data suggests that the signaling center is induced by reciprocal epithelial-mesenchymal interactions, and its induction may be independent of the enamel knot.

  6. Tissue Motion and Assembly During Early Cardiovascular Morphogenesis

    NASA Astrophysics Data System (ADS)

    Rongish, Brenda

    2010-03-01

    Conventional dogma in the field of cardiovascular developmental biology suggests that cardiac precursor cells migrate to the embryonic midline to form a tubular heart. These progenitors are believed to move relative to their extracellular matrix (ECM); responding to stimulatory and inhibitory cues in their environment. The tubular heart that is formed by 30 hours post fertilization is comprised of two concentric layers: the muscular myocardium and the endothelial-like endocardium, which are separated by a thick layer of ECM believed to be secreted predominantly by the myocardial cells. Here we describe the origin and motility of fluorescently tagged endocardial precursors in transgenic (Tie1-YFP) quail embryos (R. Lansford, Caltech) using epifluorescence time-lapse imaging. To visualize the environment of migrating endocardial progenitors, we labeled two ECM components, fibronectin and fibrillin-2, via in vivo microinjection of fluorochrome-conjugated monoclonal antibodies. Dynamic imaging was performed at stages encompassing tubular heart assembly and early looping. We established the motion of endocardial precursor cells and presumptive cardiac ECM fibrils using both object tracking and particle image velocimetry (image cross correlation). We determined the relative importance of directed cell autonomous motility versus passive tissue movements in endocardial morphogenesis. The data show presumptive endocardial cells and cardiac ECM fibrils are swept passively into the anterior and posterior poles of the elongating tubular heart. These quantitative data indicate the contribution of cell autonomous motility displayed by endocardial precursors is limited. Thus, tissue motion drives most of the cell displacements during endocardial morphogenesis.

  7. Early epithelial signaling center governs tooth budding morphogenesis.

    PubMed

    Ahtiainen, Laura; Uski, Isa; Thesleff, Irma; Mikkola, Marja L

    2016-09-12

    During organogenesis, cell fate specification and patterning are regulated by signaling centers, specialized clusters of morphogen-expressing cells. In many organs, initiation of development is marked by bud formation, but the cellular mechanisms involved are ill defined. Here, we use the mouse incisor tooth as a model to study budding morphogenesis. We show that a group of nonproliferative epithelial cells emerges in the early tooth primordium and identify these cells as a signaling center. Confocal live imaging of tissue explants revealed that although these cells reorganize dynamically, they do not reenter the cell cycle or contribute to the growing tooth bud. Instead, budding is driven by proliferation of the neighboring cells. We demonstrate that the activity of the ectodysplasin/Edar/nuclear factor κB pathway is restricted to the signaling center, and its inactivation leads to fewer quiescent cells and a smaller bud. These data functionally link the signaling center size to organ size and imply that the early signaling center is a prerequisite for budding morphogenesis. PMID:27621364

  8. Pulling together: Tissue-generated forces that drive lumen morphogenesis.

    PubMed

    Navis, Adam; Nelson, Celeste M

    2016-07-01

    Mechanical interactions are essential for bending and shaping tissues during morphogenesis. A common feature of nearly all internal organs is the formation of a tubular network consisting of an epithelium that surrounds a central lumen. Lumen formation during organogenesis requires precisely coordinated mechanical and biochemical interactions. Whereas many genetic regulators of lumen formation have been identified, relatively little is known about the mechanical cues that drive lumen morphogenesis. Lumens can be shaped by a variety of physical behaviors including wrapping a sheet of cells around a hollow core, rearranging cells to expose a lumenal cavity, or elongating a tube via cell migration, though many of the details underlying these movements remain poorly understood. It is essential to define how forces generated by individual cells cooperate to produce the tissue-level forces that drive organogenesis. Transduction of mechanical forces relies on several conserved processes including the contraction of cytoskeletal networks or expansion of lumens through increased fluid pressure. The morphogenetic events that drive lumen formation serve as a model for similar mechanical processes occurring throughout development. To understand how lumenal networks arise, it will be essential to investigate how biochemical and mechanical processes integrate to generate complex structures from comparatively simple interactions.

  9. The unfolded protein response is required for dendrite morphogenesis

    PubMed Central

    Wei, Xing; Howell, Audrey S; Dong, Xintong; Taylor, Caitlin A; Cooper, Roshni C; Zhang, Jianqi; Zou, Wei; Sherwood, David R; Shen, Kang

    2015-01-01

    Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homolog of mammalian BiP/ grp78). Surprisingly, a single transmembrane leucine-rich repeat protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors. DOI: http://dx.doi.org/10.7554/eLife.06963.001 PMID:26052671

  10. Size-dependent symmetry breaking in models for morphogenesis

    NASA Astrophysics Data System (ADS)

    Barrio, R. A.; Maini, P. K.; Aragón, J. L.; Torres, M.

    2002-08-01

    A general property of dynamical systems is the appearance of spatial and temporal patterns due to a change of stability of a homogeneous steady state. Such spontaneous symmetry breaking is observed very frequently in all kinds of real systems, including the development of shape in living organisms. Many nonlinear dynamical systems present a wide variety of patterns with different shapes and symmetries. This fact restricts the applicability of these models to morphogenesis, since one often finds a surprisingly small variation in the shapes of living organisms. For instance, all individuals in the Phylum Echinodermata share a persistent radial fivefold symmetry. In this paper, we investigate in detail the symmetry-breaking properties of a Turing reaction-diffusion system confined in a small disk in two dimensions. It is shown that the symmetry of the resulting pattern depends only on the size of the disk, regardless of the boundary conditions and of the differences in the parameters that differentiate the interior of the domain from the outer space. This study suggests that additional regulatory mechanisms to control the size of the system are of crucial importance in morphogenesis.

  11. Cytokinin signaling regulates pavement cell morphogenesis in Arabidopsis.

    PubMed

    Li, Hongjiang; Xu, Tongda; Lin, Deshu; Wen, Mingzhang; Xie, Mingtang; Duclercq, Jérôme; Bielach, Agnieszka; Kim, Jungmook; Reddy, G Venugopala; Zuo, Jianru; Benková, Eva; Friml, Jiří; Guo, Hongwei; Yang, Zhenbiao

    2013-02-01

    The puzzle piece-shaped Arabidopsis leaf pavement cells (PCs) with interdigitated lobes and indents is a good model system to investigate the mechanisms that coordinate cell polarity and shape formation within a tissue. Auxin has been shown to coordinate the interdigitation by activating ROP GTPase-dependent signaling pathways. To identify additional components or mechanisms, we screened for mutants with abnormal PC morphogenesis and found that cytokinin signaling regulates the PC interdigitation pattern. Reduction in cytokinin accumulation and defects in cytokinin signaling (such as in ARR7-over-expressing lines, the ahk3cre1 cytokinin receptor mutant, and the ahp12345 cytokinin signaling mutant) enhanced PC interdigitation, whereas over-production of cytokinin and over-activation of cytokinin signaling in an ARR20 over-expression line delayed or abolished PC interdigitation throughout the cotyledon. Genetic and biochemical analyses suggest that cytokinin signaling acts upstream of ROPs to suppress the formation of interdigitated pattern. Our results provide novel mechanistic understanding of the pathways controlling PC shape and uncover a new role for cytokinin signaling in cell morphogenesis.

  12. Evolutionary stasis in pollen morphogenesis due to natural selection.

    PubMed

    Matamoro-Vidal, Alexis; Prieu, Charlotte; Furness, Carol A; Albert, Béatrice; Gouyon, Pierre-Henri

    2016-01-01

    The contribution of developmental constraints and selective forces to the determination of evolutionary patterns is an important and unsolved question. We test whether the long-term evolutionary stasis observed for pollen morphogenesis (microsporogenesis) in eudicots is due to developmental constraints or to selection on a morphological trait shaped by microsporogenesis: the equatorial aperture pattern. Most eudicots have three equatorial apertures but several taxa have independently lost the equatorial pattern and have microsporogenesis decoupled from aperture pattern determination. If selection on the equatorial pattern limits variation, we expect to see increased variation in microsporogenesis in the nonequatorial clades. Variation of microsporogenesis was studied using phylogenetic comparative analyses in 83 species dispersed throughout eudicots including species with and without equatorial apertures. The species that have lost the equatorial pattern have highly variable microsporogenesis at the intra-individual and inter-specific levels regardless of their pollen morphology, whereas microsporogenesis remains stable in species with the equatorial pattern. The observed burst of variation upon loss of equatorial apertures shows that there are no strong developmental constraints precluding variation in microsporogenesis, and that the stasis is likely to be due principally to selective pressure acting on pollen morphogenesis because of its implication in the determination of the equatorial aperture pattern. PMID:26248868

  13. Pkd1 regulates lymphatic vascular morphogenesis during development

    PubMed Central

    Coxam, Baptiste; Sabine, Amélie; Bower, Neil I.; Smith, Kelly A.; Pichol-Thievend, Cathy; Skoczylas, Renae; Astin, Jonathan W.; Frampton, Emmanuelle; Jaquet, Muriel; Crosier, Philip S.; Parton, Robert G.; Harvey, Natasha L.; Petrova, Tatiana V.; Schulte-Merker, Stefan; Francois, Mathias; Hogan, Benjamin M.

    2016-01-01

    Lymphatic vessels arise during development through sprouting of precursor cells from veins, which is regulated by well-studied signaling and transcriptional mechanisms. Less well understood is the ongoing elaboration of vessels to form a network. This involves cell polarisation, coordinated migration, adhesion, mixing, regression and cell shape rearrangements. We identified a zebrafish mutant, lymphatic and cardiac defects 1 (lyc1), with reduced lymphatic vessel development. We found a mutation in polycystic kidney disease 1a to be responsible for the phenotype. PKD1 is the most frequently mutated gene in autosomal dominant polycystic kidney disease (ADPKD). Initial sprouting of lymphatic precursors is normal in lyc1 mutants, but ongoing migration fails. Loss of Pkd1 in mice also has no effect on sprouting of precursors but leads to failed morphogenesis of the subcutaneous lymphatic network. Individual lymphatic endothelial cells display defective polarity, elongation and adherens junctions. This work identifies a highly selective and unexpected role for Pkd1 in lymphatic vessel morphogenesis during development. PMID:24767999

  14. Vertebral numbers and human evolution.

    PubMed

    Williams, Scott A; Middleton, Emily R; Villamil, Catalina I; Shattuck, Milena R

    2016-01-01

    Ever since Tyson (1699), anatomists have noted and compared differences in the regional numbers of vertebrae among humans and other hominoids. Subsequent workers interpreted these differences in phylogenetic, functional, and behavioral frameworks and speculated on the history of vertebral numbers during human evolution. Even in a modern phylogenetic framework and with greatly expanded sample sizes of hominoid species, researchers' conclusions vary drastically, positing that hominins evolved from either a "long-backed" (numerically long lumbar column) or a "short-backed" (numerically short lumbar column) ancestor. We show that these disparate interpretations are due in part to the use of different criteria for what defines a lumbar vertebra, but argue that, regardless of which lumbar definition is used, hominins are similar to their great ape relatives in possessing a short trunk, a rare occurrence in mammals and one that defines the clade Hominoidea. Furthermore, we address the recent claim that the early hominin thoracolumbar configuration is not distinct from that of modern humans and conclude that early hominins show evidence of "cranial shifting," which might explain the anomalous morphology of several early hominin fossils. Finally, we evaluate the competing hypotheses on numbers of vertebrae and argue that the current data support a hominin ancestor with an African ape-like short trunk and lower back.

  15. Melatonin Receptor Genes in Vertebrates

    PubMed Central

    Li, Di Yan; Smith, David Glenn; Hardeland, Rüdiger; Yang, Ming Yao; Xu, Huai Liang; Zhang, Long; Yin, Hua Dong; Zhu, Qing

    2013-01-01

    Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor. PMID:23712359

  16. Rotations in a Vertebrate Setting

    NASA Astrophysics Data System (ADS)

    McCollum, Gin

    2003-05-01

    Rotational movements of the head are often considered to be measured in a single three dimensional coordinate system implemented by the semicircular canals of the vestibular system of the inner ear. However, the vertebrate body -- including the nervous system -- obeys rectangular symmetries alien to rotation groups. At best, nervous systems mimic the physical rotation group in a fragmented way, only partially reintegrating physical movements in whole organism responses. The vestibular canal reference frame is widely used in nervous systems, for example by eye movements. It is used to some extent even in the cerebrum, as evidenced by the remission of hemineglect -- in which half of space is ignored -- when the vestibular system is stimulated. However, reintegration of space by the organism remains incomplete. For example, compensatory eye movements (which in most cases aid visual fixation) may disagree with conscious self-motion perception. In addition, movement-induced nausea, illusions, and cue-free perceptions demonstrate symmetry breaking or incomplete spatial symmetries. As part of a long-term project to investigate rotation groups in nervous systems, we have analyzed the symmetry group of a primary vestibulo-spinal projection.

  17. Aging and regeneration in vertebrates.

    PubMed

    Sousounis, Konstantinos; Baddour, Joelle A; Tsonis, Panagiotis A

    2014-01-01

    Aging is marked by changes that affect organs and resident stem cell function. Shorting of telomeres, DNA damage, oxidative stress, deregulation of genes and proteins, impaired cell-cell communication, and an altered systemic environment cause the eventual demise of cells. At the same time, reparative activities also decline. It is intriguing to correlate aging with the decline of regenerative abilities. Animal models with strong regenerative capabilities imply that aging processes might not be affecting regeneration. In this review, we selectively present age-dependent changes in stem/progenitor cells that are vital for tissue homeostasis and repair. In addition, the aging effect on regeneration following injury in organs such as lung, skeletal muscle, heart, nervous system, cochlear hair, lens, and liver are discussed. These tissues are also known for diseases such as heart attack, stroke, cognitive impairment, cataract, and hearing loss that occur mostly during aging in humans. Conclusively, vertebrate regeneration declines with age with the loss of stem/progenitor cell function. Future studies on improving the function of stem cells, along with studies in fish and amphibians where regeneration does not decline with age, will undoubtedly provide insights into both processes. PMID:24512711

  18. Control of vertebrate core planar cell polarity protein localization and dynamics by Prickle 2

    PubMed Central

    Butler, Mitchell T.; Wallingford, John B.

    2015-01-01

    Planar cell polarity (PCP) is a ubiquitous property of animal tissues and is essential for morphogenesis and homeostasis. In most cases, this fundamental property is governed by a deeply conserved set of ‘core PCP’ proteins, which includes the transmembrane proteins Van Gogh-like (Vangl) and Frizzled (Fzd), as well as the cytoplasmic effectors Prickle (Pk) and Dishevelled (Dvl). Asymmetric localization of these proteins is thought to be central to their function, and understanding the dynamics of these proteins is an important challenge in developmental biology. Among the processes that are organized by the core PCP proteins is the directional beating of cilia, such as those in the vertebrate node, airway and brain. Here, we exploit the live imaging capabilities of Xenopus to chart the progressive asymmetric localization of fluorescent reporters of Dvl1, Pk2 and Vangl1 in a planar polarized ciliated epithelium. Using this system, we also characterize the influence of Pk2 on the asymmetric dynamics of Vangl1 at the cell cortex, and we define regions of Pk2 that control its own localization and those impacting Vangl1. Finally, our data reveal a striking uncoupling of Vangl1 and Dvl1 asymmetry. This study advances our understanding of conserved PCP protein functions and also establishes a rapid, tractable platform to facilitate future in vivo studies of vertebrate PCP protein dynamics. PMID:26293301

  19. Vangl2 cooperates with Rab11 and Myosin V to regulate apical constriction during vertebrate gastrulation

    PubMed Central

    Ossipova, Olga; Chuykin, Ilya; Chu, Chih-Wen; Sokol, Sergei Y.

    2015-01-01

    Core planar cell polarity (PCP) proteins are well known to regulate polarity in Drosophila and vertebrate epithelia; however, their functions in vertebrate morphogenesis remain poorly understood. In this study, we describe a role for PCP signaling in the process of apical constriction during Xenopus gastrulation. The core PCP protein Vangl2 is detected at the apical surfaces of cells at the blastopore lip, and it functions during blastopore formation and closure. Further experiments show that Vangl2, as well as Daam1 and Rho-associated kinase (Rock), regulate apical constriction of bottle cells at the blastopore and ectopic constriction of ectoderm cells triggered by the actin-binding protein Shroom3. At the blastopore lip, Vangl2 is required for the apical accumulation of the recycling endosome marker Rab11. We also show that Rab11 and the associated motor protein Myosin V play essential roles in both endogenous and ectopic apical constriction, and might be involved in Vangl2 trafficking to the cell surface. Overexpression of Rab11 RNA was sufficient to partly restore normal blastopore formation in Vangl2-deficient embryos. These observations suggest that Vangl2 affects Rab11 to regulate apical constriction during blastopore formation. PMID:25480917

  20. Stepwise maturation of apicobasal polarity of the neuroepithelium is essential for vertebrate neurulation.

    PubMed

    Yang, Xiaojun; Zou, Jian; Hyde, David R; Davidson, Lance A; Wei, Xiangyun

    2009-09-16

    During vertebrate neurulation, extensive cell movements transform the flat neural plate into the neural tube. This dynamic morphogenesis requires the tissue to bear a certain amount of plasticity to accommodate shape and position changes of individual cells as well as intercellular cohesiveness to maintain tissue integrity and architecture. For most of the neural plate-neural tube transition, cells are polarized along the apicobasal axis. The establishment and maintenance of this polarity requires many polarity proteins that mediate cell-cell adhesion either directly or indirectly. Intercellular adhesion reduces tissue plasticity and enhances tissue integrity. However, it remains unclear how apicobasal polarity is regulated to meet the opposing needs for tissue plasticity and tissue integrity during neurulation. Here, we show that N-Cad/ZO-1 complex-initiated apicobasal polarity is stabilized by the late-onsetting Lin7c/Nok complex after the extensive morphogenetic cell movements in neurulation. Loss of either N-Cad or Lin7c disrupts neural tube formation. Furthermore, precocious overexpression of Lin7c induces multiaxial mirror symmetry in zebrafish neurulation. Our data suggest that stepwise maturation of apicobasal polarity plays an essential role in vertebrate neurulation.

  1. Stepwise maturation of apicobasal polarity of the neuroepithelium is essential for vertebrate neurulation

    PubMed Central

    Yang, Xiaojun; Zou, Jian; Hyde, David R.; Davidson, Lance A.; Wei, Xiangyun

    2009-01-01

    During vertebrate neurulation, extensive cell movements transform the flat neural plate into the neural tube. This dynamic morphogenesis requires the tissue to bear a certain amount of plasticity to accommodate shape and position changes of individual cells as well as intercellular cohesiveness to maintain tissue integrity and architecture. For most of the neural plate - neural tube transition, cells are polarized along the apicobasal axis. The establishment and maintenance of this polarity requires many polarity proteins that mediate cell-cell adhesion either directly or indirectly. Intercellular adhesion reduces tissue plasticity and enhances tissue integrity. However, it remains unclear how apicobasal polarity is regulated to meet the opposing needs for tissue plasticity and tissue integrity during neurulation. Here, we show that N-Cad/ZO-1 complex-initiated apicobasal polarity is stabilized by the late-onsetting Lin7c/Nok complex after the extensive morphogenetic cell movements in neurulation. Loss of either N-Cad or Lin7c disrupts neural tube formation. Furthermore, precocious overexpression of Lin7c induces multiaxial mirror symmetry in zebrafish neurulation. Our data suggest that stepwise maturation of apicobasal polarity plays an essential role in vertebrate neurulation. PMID:19759292

  2. RFamide Peptides in Early Vertebrate Development

    PubMed Central

    Sandvik, Guro Katrine; Hodne, Kjetil; Haug, Trude Marie; Okubo, Kataaki; Weltzien, Finn-Arne

    2014-01-01

    RFamides (RFa) are neuropeptides involved in many different physiological processes in vertebrates, such as reproductive behavior, pubertal activation of the reproductive endocrine axis, control of feeding behavior, and pain modulation. As research has focused mostly on their role in adult vertebrates, the possible roles of these peptides during development are poorly understood. However, the few studies that exist show that RFa are expressed early in development in different vertebrate classes, perhaps mostly associated with the central nervous system. Interestingly, the related peptide family of FMRFa has been shown to be important for brain development in invertebrates. In a teleost, the Japanese medaka, knockdown of genes in the Kiss system indicates that Kiss ligands and receptors are vital for brain development, but few other functional studies exist. Here, we review the literature of RFa in early vertebrate development, including the possible functional roles these peptides may play. PMID:25538682

  3. A Case of Aerococcus Urinae Vertebral Osteomyelitis

    PubMed Central

    Jerome, Michael; Slim, Jihad; Sison, Raymund; Marton, Randy

    2015-01-01

    Aerococcus urinae is an aerobic, alpha hemolytic gram positive coccus bacterium that grows in pairs or clusters. We report the first case of vertebral osteomyelitis due to A. urinae. This has not been previously reported in the literature. PMID:26069429

  4. Sleep and orexins in nonmammalian vertebrates.

    PubMed

    Volkoff, Hélène

    2012-01-01

    Although a precise definition of "sleep" has yet to be established, sleep-like behaviors have been observed in all animals studied to date including mammals and nonmammalian vertebrates. Orexins are hypothalamic neuropeptides that are involved in the regulation of many physiological functions, including feeding, thermoregulation, cardiovascular control, as well as the control of the sleep-wakefulness cycle. To date, the knowledge on the functions of orexins in nonmammalian vertebrates is still limited, but the similarity of the structures of orexins and their receptors among vertebrates suggest that they have similar conserved physiological functions. This review describes our current knowledge on sleep in nonmammalian vertebrates (birds, reptiles, amphibians, and fish) and the possible role of orexins in the regulation of their energy homeostasis and arousal states. PMID:22640621

  5. Cadherins and catenins in dendrite and synapse morphogenesis

    PubMed Central

    Seong, Eunju; Yuan, Li; Arikkath, Jyothi

    2015-01-01

    Neurons are highly polarized specialized cells. Neuronal integrity and functional roles are critically dependent on dendritic architecture and synaptic structure, function and plasticity. The cadherins are glycosylated transmembrane proteins that form cell adhesion complexes in various tissues. They are associated with a group of cytosolic proteins, the catenins. While the functional roles of the complex have been extensively investigates in non-neuronal cells, it is becoming increasingly clear that components of the complex have critical roles in regulating dendritic and synaptic architecture, function and plasticity in neurons. Consistent with these functional roles, aberrations in components of the complex have been implicated in a variety of neurodevelopmental disorders. In this review, we discuss the roles of the classical cadherins and catenins in various aspects of dendrite and synapse architecture and function and their relevance to human neurological disorders. Cadherins are glycosylated transmembrane proteins that were initially identified as Ca2+-dependent cell adhesion molecules. They are present on plasma membrane of a variety of cell types from primitive metazoans to humans. In the past several years, it has become clear that in addition to providing mechanical adhesion between cells, cadherins play integral roles in tissue morphogenesis and homeostasis. The cadherin family is composed of more than 100 members and classified into several subfamilies, including classical cadherins and protocadherins. Several of these cadherin family members have been implicated in various aspects of neuronal development and function.1-3 The classical cadherins are associated with a group of cytosolic proteins, collectively called the catenins. While the functional roles of the cadherin-catenin cell adhesion complex have been extensively investigated in epithelial cells, it is now clear that components of the complex are well expressed in central neurons at different

  6. Radiotherapy in the treatment of vertebral hemangiomas

    SciTech Connect

    Faria, S.L.; Schlupp, W.R.; Chiminazzo, H. Jr.

    1985-02-01

    Symptomatic vertebral hemangiomas are not common. Although radiotherapy has been used as treatment, the data are sparse concerning total dose, fractionation and results. The authors report nine patients with vertebral hemangioma treated with 3000-4000 rad, 200 rad/day, 5 fractions per week, followed from 6 to 62 months. Seventy-seven percent had complete or almost complete disappearance of the symptoms. Radiotherapy schedules are discussed.

  7. Vertebrate Cells Express Protozoan Antigen after Hybridization

    NASA Astrophysics Data System (ADS)

    Crane, Mark St. J.; Dvorak, James A.

    1980-04-01

    Epimastigotes, the invertebrate host stage of Trypanosoma cruzi, the protozoan parasite causing Chagas' disease in man, were fused with vertebrate cells by using polyethylene glycol. Hybrid cells were selected on the basis of T. cruzi DNA complementation of biochemical deficiencies in the vertebrate cells. Some clones of the hybrid cells expressed T. cruzi-specific antigen. It might be possible to use selected antigens obtained from the hybrids as vaccines for immunodiagnosis or for elucidation of the pathogenesis of Chagas' disease.

  8. Percutaneous Vertebral Body Augmentation: An Updated Review

    PubMed Central

    Omidi-Kashani, Farzad

    2014-01-01

    There are many medical conditions like osteoporosis, tumor, or osteonecrosis that weaken the structural strength of the vertebral body and prone it to fracture. Percutaneous vertebral augmentation that is usually applied by polymethylmethacrylate is a relatively safe, effective, and long lasting procedure commonly performed in these situations. In this paper, we updated a review of biomechanics, indications, contraindications, surgical techniques, complications, and overall prognosis of these minimally invasive spinal procedures. PMID:25379561

  9. Role of Transpedicular Percutaneous Vertebral Biopsy for Diagnosis of Pathology in Vertebral Compression Fractures

    PubMed Central

    Nadkarni, Sunil; Hardikar, Sharad Moreshwar; Hardikar, Madan Sharad

    2016-01-01

    Study Design Retrospective observational study. Purpose To identify the role of percutaneous vertebral biopsy in histopathological diagnosis of vertebral compression fractures and to identify the frequency of unexpected malignancy in vertebral compression fractures. Overview of Literature Vertebral compression fractures are common in the Indian population. Magnetic resonance imaging and nuclear imaging have some limitations in the diagnosis of definitive pathology of vertebral compression fractures. Therefore, histological confirmation is necessary for definitive diagnosis and to plan appropriate management for patient. Methods A retrospective observational study was conducted involving 84 patients who underwent percutaneous vertebral biopsy between 2010 and 2014. We performed C-arm guided percutaneous transpedicular core vertebral biopsy of vertebral compression fractures under combination of local anesthesia and intravenous conscious sedation. Results Sufficient biopsy material was obtained in 79 of the 84 cases. In the other five cases, biopsy material was not sufficient for reporting. Out of the 79 cases, osteoporotic pathology was detected in 69 patients, malignancy was detected in 8 patients and no pathology was found in 2 patients. Two patients with distant metastases to vertebra were identified. Primary spinal malignancy was detected in 6 patients (1 unsuspected plasmacytoma, 5 diagnosed malignancy preoperatively). So, the frequency of unsuspected malignancy of this study was 1.19% (1/84). None of the patients had any complications. Conclusions C-arm guided percutaneous transpedicular vertebral biopsy is useful in obtaining definitive histopathological diagnosis of vertebral compression fractures, especially in differentiating malignant and non-malignant vertebral compression fractures and helping plan appropriate management of patients. The rate of unexpected malignancy in vertebral compression fracture was 1.19%. PMID:27790322

  10. Post-embryonic nerve-associated precursors to adult pigment cells: genetic requirements and dynamics of morphogenesis and differentiation.

    PubMed

    Budi, Erine H; Patterson, Larissa B; Parichy, David M

    2011-05-01

    The pigment cells of vertebrates serve a variety of functions and generate a stunning variety of patterns. These cells are also implicated in human pathologies including melanoma. Whereas the events of pigment cell development have been studied extensively in the embryo, much less is known about morphogenesis and differentiation of these cells during post-embryonic stages. Previous studies of zebrafish revealed genetically distinct populations of embryonic and adult melanophores, the ectotherm homologue of amniote melanocytes. Here, we use molecular markers, vital labeling, time-lapse imaging, mutational analyses, and transgenesis to identify peripheral nerves as a niche for precursors to adult melanophores that subsequently migrate to the skin to form the adult pigment pattern. We further identify genetic requirements for establishing, maintaining, and recruiting precursors to the adult melanophore lineage and demonstrate novel compensatory behaviors during pattern regulation in mutant backgrounds. Finally, we show that distinct populations of latent precursors having differential regenerative capabilities persist into the adult. These findings provide a foundation for future studies of post-embryonic pigment cell precursors in development, evolution, and neoplasia.

  11. The Pitx2c N-terminal domain is a critical interaction domain required for asymmetric morphogenesis

    PubMed Central

    Simard, Annie; Di Giorgio, Luciano; Amen, Melanie; Westwood, Ashley; Amendt, Brad A.; Ryan, Aimee K.

    2010-01-01

    The paired-like homeodomain transcription factor Pitx2c has an essential role in patterning the left-right axis. However, neither its transcriptional targets nor the molecular mechanisms through which it exerts its patterning function are known. Here we provide evidence that the N-terminal domain of Pitx2c is important for this activity. Overexpression of the Pitx2c N-terminus in ovo randomizes the direction of heart looping, the first morphological asymmetry conserved in vertebrate embryos. In addition, the Pitx2c N-terminal domain blocks the ability of Pitx2c to synergize with Nkx2.5 to transactivate the procollagen lysyl hydroxylase (Plod-1) promoter in transient transfection assays. A five amino acid region containing leucine-41 is required for both of these effects. Our data suggest that the Pitx2c N-terminal domain competes with endogenous Pitx2c for binding to a protein interaction partner that is required for the activation of genes that direct asymmetric morphogenesis along the left-right axis. PMID:19681163

  12. Eye morphogenesis driven by epithelial flow into the optic cup facilitated by modulation of bone morphogenetic protein

    PubMed Central

    Heermann, Stephan; Schütz, Lucas; Lemke, Steffen; Krieglstein, Kerstin; Wittbrodt, Joachim

    2015-01-01

    The hemispheric, bi-layered optic cup forms from an oval optic vesicle during early vertebrate eye development through major morphological transformations. The overall basal surface, facing the developing lens, is increasing, while, at the same time, the space basally occupied by individual cells is decreasing. This cannot be explained by the classical view of eye development. Using zebrafish (Danio rerio) as a model, we show that the lens-averted epithelium functions as a reservoir that contributes to the growing neuroretina through epithelial flow around the distal rims of the optic cup. We propose that this flow couples morphogenesis and retinal determination. Our 4D data indicate that future stem cells flow from their origin in the lens-averted domain of the optic vesicle to their destination in the ciliary marginal zone. BMP-mediated inhibition of the flow results in ectopic neuroretina in the RPE domain. Ultimately the ventral fissure fails to close resulting in coloboma. DOI: http://dx.doi.org/10.7554/eLife.05216.001 PMID:25719386

  13. Retroviral Diversity and Distribution in Vertebrates

    PubMed Central

    Herniou, Elisabeth; Martin, Joanne; Miller, Karen; Cook, James; Wilkinson, Mark; Tristem, Michael

    1998-01-01

    We used the PCR to screen for the presence of endogenous retroviruses within the genomes of 18 vertebrate orders across eight classes, concentrating on reptilian, amphibian, and piscine hosts. Thirty novel retroviral sequences were isolated and characterized by sequencing approximately 1 kb of their encoded protease and reverse transcriptase genes. Isolation of novel viruses from so many disparate hosts suggests that retroviruses are likely to be ubiquitous within all but the most basal vertebrate classes and, furthermore, gives a good indication of the overall retroviral diversity within vertebrates. Phylogenetic analysis demonstrated that viruses clustering with (but not necessarily closely related to) the spumaviruses and murine leukemia viruses are widespread and abundant in vertebrate genomes. In contrast, we were unable to identify any viruses from hosts outside of mammals and birds which grouped with the other five currently recognized retroviral genera: the lentiviruses, human T-cell leukemia-related viruses, avian leukemia virus-related retroviruses, type D retroviruses, and mammalian type B retroviruses. There was also some indication that viruses isolated from individual vertebrate classes tended to cluster together in phylogenetic reconstructions. This implies that the horizontal transmission of at least some retroviruses, between some vertebrate classes, occurs relatively infrequently. It is likely that many of the retroviral sequences described here are distinct enough from those of previously characterized viruses to represent novel retroviral genera. PMID:9621058

  14. Evolution and development of the vertebrate neck

    PubMed Central

    Ericsson, Rolf; Knight, Robert; Johanson, Zerina

    2013-01-01

    Muscles of the vertebrate neck include the cucullaris and hypobranchials. Although a functional neck first evolved in the lobe-finned fishes (Sarcopterygii) with the separation of the pectoral/shoulder girdle from the skull, the neck muscles themselves have a much earlier origin among the vertebrates. For example, lampreys possess hypobranchial muscles, and may also possess the cucullaris. Recent research in chick has established that these two muscles groups have different origins, the hypobranchial muscles having a somitic origin but the cucullaris muscle deriving from anterior lateral plate mesoderm associated with somites 1–3. Additionally, the cucullaris utilizes genetic pathways more similar to the head than the trunk musculature. Although the latter results are from experiments in the chick, cucullaris homologues occur in a variety of more basal vertebrates such as the sharks and zebrafish. Data are urgently needed from these taxa to determine whether the cucullaris in these groups also derives from lateral plate mesoderm or from the anterior somites, and whether the former or the latter represent the basal vertebrate condition. Other lateral plate mesoderm derivatives include the appendicular skeleton (fins, limbs and supporting girdles). If the cucullaris is a definitive lateral plate-derived structure it may have evolved in conjunction with the shoulder/limb skeleton in vertebrates and thereby provided a greater degree of flexibility to the heads of predatory vertebrates. PMID:22697305

  15. The origins of colour vision in vertebrates.

    PubMed

    Collin, Shaun P; Trezise, Ann E O

    2004-07-01

    The capacity for colour vision is mediated by the comparison of the signal intensities from photoreceptors of two or more types that differ in spectral sensitivity. Morphological, physiological and molecular analyses of the retina in an agnathan (jawless) fish, the lamprey Geotria australis, may hold important clues to the origins of colour vision in vertebrates. Lampreys are extant representatives of an ancient group of vertebrates, the origins of which are thought to date back to at least the early Cambrian, approximately 540 million years ago. G. australis possesses five photoreceptor types, each with cone-like ultrastructural features and different spectral sensitivities. Recent molecular genetic studies have also revealed that five visual pigment (opsin) genes are expressed in the retina, each of which is orthologous to the major classes of vertebrate opsin genes. These findings reveal that multiple opsin genes originated very early in vertebrate evolution, prior to the separation of the jawed and jawless vertebrate lineages, thereby providing the genetic basis for colour vision in all vertebrates.

  16. Giant ankyrin-G: a critical innovation in vertebrate evolution of fast and integrated neuronal signaling.

    PubMed

    Jenkins, Paul M; Kim, Namsoo; Jones, Steven L; Tseng, Wei Chou; Svitkina, Tatyana M; Yin, Henry H; Bennett, Vann

    2015-01-27

    Axon initial segments (AISs) and nodes of Ranvier are sites of clustering of voltage-gated sodium channels (VGSCs) in nervous systems of jawed vertebrates that facilitate fast long-distance electrical signaling. We demonstrate that proximal axonal polarity as well as assembly of the AIS and normal morphogenesis of nodes of Ranvier all require a heretofore uncharacterized alternatively spliced giant exon of ankyrin-G (AnkG). This exon has sequence similarity to I-connectin/Titin and was acquired after the first round of whole-genome duplication by the ancestral ANK2/ANK3 gene in early vertebrates before development of myelin. The giant exon resulted in a new nervous system-specific 480-kDa polypeptide combining previously known features of ANK repeats and β-spectrin-binding activity with a fibrous domain nearly 150 nm in length. We elucidate previously undescribed functions for giant AnkG, including recruitment of β4 spectrin to the AIS that likely is regulated by phosphorylation, and demonstrate that 480-kDa AnkG is a major component of the AIS membrane "undercoat' imaged by platinum replica electron microscopy. Surprisingly, giant AnkG-knockout neurons completely lacking known AIS components still retain distal axonal polarity and generate action potentials (APs), although with abnormal frequency. Giant AnkG-deficient mice live to weaning and provide a rationale for survival of humans with severe cognitive dysfunction bearing a truncating mutation in the giant exon. The giant exon of AnkG is required for assembly of the AIS and nodes of Ranvier and was a transformative innovation in evolution of the vertebrate nervous system that now is a potential target in neurodevelopmental disorders.

  17. Morphogenesis and bioluminescence in germination of red bean

    NASA Astrophysics Data System (ADS)

    Kai, Shoichi; Mitani, Tomohiko; Fujikawa, Masahiro

    1994-10-01

    Spontaneous bioluminescence and morphogenesis were investigated for the germination and the growth processes of a red bean seed under suppression of photosynthesis. Three types of shape in seed growth were observed in well controlled conditions: (1) no root hair and leaves, (2) with root hairs and leaves and (3) no root growth. In this article, growth dynamics for the first case was investigated. The average growth dynamics of the root length of a red bean after germination and its variance were well described by a simple logistic equation with a noise term. It was observed that the scaling property for the growth dynamics has held. Strong luminescence was observed at two inflection points of the logistic curve of the root growth. By the use of a two dimensional photon counting method, it was clarified that the strong emission was mainly radiated from the cell division zone near a root cap and rather less emission from an elongation area.

  18. [The morphogenesis of mammalian cutaneous glands in evolutionary perspective].

    PubMed

    Chernova, O F

    2012-01-01

    The morphogenesis of mammalian cutaneous glands is considered based on the analysis of the literature and our own original data with the focus on the issues of gland polymorphism and specific features in postnatal development (from the case study of circumanal hepatoid glands of newborn domestic dogs), including the features reflecting the evolutionary relationships of various types of cutaneous glands. The hepatoid glands are a component of the glandular complex ofthe hair follicle, which also includes sebaceous and sweat glands; have a specific structure; and produce protein secretion by a merocrine pathway. Characteristic of these glands are wide polymorphism, sex- and age-related differences in the degree of development, occurrence in only a few phylogenetically related mammalian taxa (even-toed ungulates and carnivores); and a signaling type of their secretion. The data support the "generative concept," relying on the idea of a separate and independent origination of diverse derivatives of the external integuments. PMID:22679770

  19. Forces for Morphogenesis Investigated with Laser Microsurgery and Quantitative Modeling

    NASA Astrophysics Data System (ADS)

    Hutson, M. Shane; Tokutake, Yoichiro; Chang, Ming-Shien; Bloor, James W.; Venakides, Stephanos; Kiehart, Daniel P.; Edwards, Glenn S.

    2003-04-01

    We investigated the forces that connect the genetic program of development to morphogenesis in Drosophila. We focused on dorsal closure, a powerful model system for development and wound healing. We found that the bulk of progress toward closure is driven by contractility in supracellular ``purse strings'' and in the amnioserosa, whereas adhesion-mediated zipping coordinates the forces produced by the purse strings and is essential only for the end stages. We applied quantitative modeling to show that these forces, generated in distinct cells, are coordinated in space and synchronized in time. Modeling of wild-type and mutant phenotypes is predictive; although closure in myospheroid mutants ultimately fails when the cell sheets rip themselves apart, our analysis indicates that βPS integrin has an earlier, important role in zipping.

  20. Theoretical model for morphogenesis and cell sorting in Dictyostelium discoideum

    NASA Astrophysics Data System (ADS)

    Umeda, T.; Inouye, K.

    1999-02-01

    The morphogenetic movement and cell sorting in cell aggregates from the mound stage to the migrating slug stage of the cellular slime mold Dictyostelium discoideum were studied using a mathematical model. The model postulates that the motive force generated by the cells is in equilibrium with the internal pressure and mechanical resistance. The moving boundary problem derived from the force balance equation and the continuity equation has stationary solutions in which the aggregate takes the shape of a spheroid (or an ellipse in two-dimensional space) with the pacemaker at one of its foci, moving at a constant speed. Numerical calculations in two-dimensional space showed that an irregularly shaped aggregate changes its shape to become an ellipse as it moves. Cell aggregates consisting of two cell types differing in motive force exhibit cell sorting and become elongated, suggesting the importance of prestalk/prespore differentiation in the morphogenesis of Dictyostelium.

  1. Testing Turing’s theory of morphogenesis in chemical cells

    PubMed Central

    Tompkins, Nathan; Li, Ning; Girabawe, Camille; Heymann, Michael; Ermentrout, G. Bard; Epstein, Irving R.; Fraden, Seth

    2014-01-01

    Alan Turing, in “The Chemical Basis of Morphogenesis” [Turing AM (1952) Philos Trans R Soc Lond 237(641):37–72], described how, in circular arrays of identical biological cells, diffusion can interact with chemical reactions to generate up to six periodic spatiotemporal chemical structures. Turing proposed that one of these structures, a stationary pattern with a chemically determined wavelength, is responsible for differentiation. We quantitatively test Turing’s ideas in a cellular chemical system consisting of an emulsion of aqueous droplets containing the Belousov–Zhabotinsky oscillatory chemical reactants, dispersed in oil, and demonstrate that reaction-diffusion processes lead to chemical differentiation, which drives physical morphogenesis in chemical cells. We observe five of the six structures predicted by Turing. In 2D hexagonal arrays, a seventh structure emerges, incompatible with Turing’s original model, which we explain by modifying the theory to include heterogeneity. PMID:24616508

  2. Emergence, self-organization and morphogenesis in biological structures.

    PubMed

    Dobrescu, R; Purcarea, V I

    2011-01-01

    The paper discusses the connection between emergence, pattern formation and nonlinear dynamics, focusing on the similarity between discrete patterns and fractal structures, and then describes different solutions to model reaction-diffusion systems as representative processes in morphogenesis. A specific example is the diffusion limited aggregation growth process, illustrated by the simulation of the evolution of a bacterial colony that shows the roles of instability and sensitivity in non-equilibrium pattern formation. Based on this particular case, it is shown how self-organization could be achieved from non-organized agglomeration of separate entities, in a region of space. We conclude with some brief remarks about universality, predictability and long-term prospects for this field of research. PMID:21505578

  3. Chemical morphogenesis: turing patterns in an experimental chemical system.

    PubMed

    Dulos, E; Boissonade, J; Perraud, J J; Rudovics, B; De Kepper, P

    1996-11-01

    Patterns resulting from the sole interplay between reaction and diffusion are probably involved in certain stages of morphogenesis in biological systems, as initially proposed by Alan Turing. Self-organization phenomena of this type can only develop in nonlinear systems (i.e. involving positive and negative feedback loops) maintained far from equilibrium. We present Turing patterns experimentally observed in a chemical system. An oscillating chemical reaction, the CIMA reaction, is operated in an open spatial reactor designed in order to obtain a pure reaction-diffusion system. The two types of Turing patterns observed, hexagonal arrays of spots and parallel stripes, are characterized by an intrinsic wavelength. We identify the origin of the necessary diffusivity between activator and inhibitor. We also describe a pattern growth mechanism by spot splitting that recalls cell division.

  4. Chemical morphogenesis: turing patterns in an experimental chemical system.

    PubMed

    Dulos, E; Boissonade, J; Perraud, J J; Rudovics, B; De Kepper, P

    1996-11-01

    Patterns resulting from the sole interplay between reaction and diffusion are probably involved in certain stages of morphogenesis in biological systems, as initially proposed by Alan Turing. Self-organization phenomena of this type can only develop in nonlinear systems (i.e. involving positive and negative feedback loops) maintained far from equilibrium. We present Turing patterns experimentally observed in a chemical system. An oscillating chemical reaction, the CIMA reaction, is operated in an open spatial reactor designed in order to obtain a pure reaction-diffusion system. The two types of Turing patterns observed, hexagonal arrays of spots and parallel stripes, are characterized by an intrinsic wavelength. We identify the origin of the necessary diffusivity between activator and inhibitor. We also describe a pattern growth mechanism by spot splitting that recalls cell division. PMID:8953211

  5. Brassinosteroid Levels Increase Drastically Prior to Morphogenesis of Tracheary Elements

    PubMed Central

    Yamamoto, Ryo; Fujioka, Shozo; Demura, Taku; Takatsuto, Suguru; Yoshida, Shigeo; Fukuda, Hiroo

    2001-01-01

    As the first step toward understanding the involvement of endogenous brassinosteroids (BRs) in cytodifferentiation, we analyzed biosynthetic activities of BRs in zinnia (Zinnia elegans L. cv Canary Bird) cells differentiating into tracheary elements. The results of feeding experiments suggested that both the early and late C6-oxidation pathways occur during tracheary element differentiation. Gas chromatography-mass spectrometry analysis revealed that five BRs, castasterone, typhasterol, 6-deoxocastasterone, 6-deoxotyphasterol, and 6-deoxoteasterone, actually existed in cultured zinnia cells and culture medium. Quantification of endogenous BRs in each stage of tracheary element differentiation by gas chromatography-mass spectrometry exhibited that they increased dramatically prior to the morphogenesis, which was consistent with the idea that BRs are necessary for the initiation of the final stage of tracheary element differentiation. Moreover, the proportion of each BR in culture medium was quite different from that in cells, suggesting that specific BRs are selectively secreted into medium and may function outside the cells. PMID:11161013

  6. Involvement of actin filaments in rhizoid morphogenesis of Spirogyra.

    PubMed

    Yoshida, Katsuhisa; Shimmen, Teruo

    2009-01-01

    The role of actin filaments in rhizoid morphogenesis was studied in Spirogyra. When the algal filaments were severed, new terminal cells started tip growth and finally formed rhizoids. Actin inhibitors, latrunculin B and cytochalasin D, reversibly inhibited the process. A mesh-like structure of actin filaments (AFs) was formed at the tip region. Gd(3+) inhibited tip growth and decreased AFs in the tip region. Either a decrease in turgor pressure or lowering of the external Ca(2+) concentration also induced similar results. It was suggested that the mesh-like AF structure is indispensable for the elongation of rhizoids. A possible organization mechanism of the mesh-like AF structure was discussed.

  7. Electron microscopy: essentials for viral structure, morphogenesis and rapid diagnosis.

    PubMed

    Zhang, Ying; Hung, Tao; Song, Jingdong; He, Jinsheng

    2013-05-01

    Electron microscopy (EM) should be used in the front line for detection of agents in emergencies and bioterrorism, on accounts of its speed and accuracy. However, the number of EM diagnostic laboratories has decreased considerably and an increasing number of people encounter difficulties with EM results. Therefore, the research on viral structure and morphologyant in EM diagnostic practice. EM has several technological advantages, and should be a fundamental tool in clinical diagnosis of viruses, particularly when agents are unknown or unsuspected. In this article, we review the historical contribution of EM to virology, and its use in virus differentiation, localization of specific virus antigens, virus-cell interaction, and viral morphogenesis. It is essential that EM investigations are based on clinical and comprehensive pathogenesis data from light or confocal microscopy. Furthermore, avoidance of artifacts or false results is necessary to exploit fully the advantages while minimizing its limitations.

  8. Force and compliance: rethinking morphogenesis in walled cells.

    PubMed

    Harold, Franklin M

    2002-12-01

    In the turgid cells of plants, protists, fungi, and bacteria, walls resist swelling; they also confer shape on the cell. These two functions are not unrelated: cell physiologists have generally agreed that morphogenesis turns on the deformation of existing wall and the deposition of new wall, while turgor pressure produces the work of expansion. In 1990, I summed up consensus in a phrase: "localized compliance with the global force of turgor pressure." My purpose here is to survey the impact of recent discoveries on the traditional conceptual framework. Topics include the recognition of a cytoskeleton in bacteria; the tide of information and insight about budding in yeast; the role of the Spitzenkörper in hyphal extension; calcium ions and actin dynamics in shaping a tip; and the interplay of protons, expansins and cellulose fibrils in cells of higher plants.

  9. An Optogenetic Method to Modulate Cell Contractility during Tissue Morphogenesis

    PubMed Central

    Guglielmi, Giorgia; Barry, Joseph D.; Huber, Wolfgang; De Renzis, Stefano

    2015-01-01

    Summary Morphogenesis of multicellular organisms is driven by localized cell shape changes. How, and to what extent, changes in behavior in single cells or groups of cells influence neighboring cells and large-scale tissue remodeling remains an open question. Indeed, our understanding of multicellular dynamics is limited by the lack of methods allowing the modulation of cell behavior with high spatiotemporal precision. Here, we developed an optogenetic approach to achieve local modulation of cell contractility and used it to control morphogenetic movements during Drosophila embryogenesis. We show that local inhibition of apical constriction is sufficient to cause a global arrest of mesoderm invagination. By varying the spatial pattern of inhibition during invagination, we further demonstrate that coordinated contractile behavior responds to local tissue geometrical constraints. Together, these results show the efficacy of this optogenetic approach to dissect the interplay between cell-cell interaction, force transmission, and tissue geometry during complex morphogenetic processes. PMID:26777292

  10. The green seaweed Ulva: a model system to study morphogenesis.

    PubMed

    Wichard, Thomas; Charrier, Bénédicte; Mineur, Frédéric; Bothwell, John H; Clerck, Olivier De; Coates, Juliet C

    2015-01-01

    Green macroalgae, mostly represented by the Ulvophyceae, the main multicellular branch of the Chlorophyceae, constitute important primary producers of marine and brackish coastal ecosystems. Ulva or sea lettuce species are some of the most abundant representatives, being ubiquitous in coastal benthic communities around the world. Nonetheless the genus also remains largely understudied. This review highlights Ulva as an exciting novel model organism for studies of algal growth, development and morphogenesis as well as mutualistic interactions. The key reasons that Ulva is potentially such a good model system are: (i) patterns of Ulva development can drive ecologically important events, such as the increasing number of green tides observed worldwide as a result of eutrophication of coastal waters, (ii) Ulva growth is symbiotic, with proper development requiring close association with bacterial epiphytes, (iii) Ulva is extremely developmentally plastic, which can shed light on the transition from simple to complex multicellularity and (iv) Ulva will provide additional information about the evolution of the green lineage.

  11. Mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling

    PubMed Central

    Sennett, Rachel; Rendl, Michael

    2012-01-01

    Embryonic hair follicle induction and formation are regulated by mesenchymal-epithelial interactions between specialized dermal cells and epidermal stem cells that switch to a hair fate. Similarly, during postnatal hair growth, communication between mesenchymal dermal papilla cells and surrounding epithelial matrix cells coordinates hair shaft production. Adult hair follicle regeneration in the hair cycle again is thought to be controlled by activating signals originating from the mesenchymal compartment and acting on hair follicle stem cells. Although many signaling pathways are implicated in hair follicle formation and growth, the precise nature, timing, and intersection of these inductive and regulatory signals remains elusive. The goal of this review is to summarize our current understanding and to discuss recent new insights into mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling. PMID:22960356

  12. hnRNP Q regulates Cdc42-mediated neuronal morphogenesis.

    PubMed

    Chen, Hung-Hsi; Yu, Hsin-I; Chiang, Wen-Cheng; Lin, Yu-De; Shia, Ben-Chang; Tarn, Woan-Yuh

    2012-06-01

    The RNA-binding protein hnRNP Q has been implicated in neuronal mRNA metabolism. Here, we show that knockdown of hnRNP Q increased neurite complexity in cultured rat cortical neurons and induced filopodium formation in mouse neuroblastoma cells. Reexpression of hnRNP Q1 in hnRNP Q-depleted cells abrogated the morphological changes of neurites, indicating a specific role for hnRNP Q1 in neuronal morphogenesis. A search for mRNA targets of hnRNP Q1 identified functionally coherent sets of mRNAs encoding factors involved in cellular signaling or cytoskeletal regulation and determined its preferred binding sequences. We demonstrated that hnRNP Q1 bound to a set of identified mRNAs encoding the components of the actin nucleation-promoting Cdc42/N-WASP/Arp2/3 complex and was in part colocalized with Cdc42 mRNA in granules. Using subcellular fractionation and immunofluorescence, we showed that knockdown of hnRNP Q reduced the level of some of those mRNAs in neurites and redistributed their encoded proteins from neurite tips to soma to different extents. Overexpression of dominant negative mutants of Cdc42 or N-WASP compromised hnRNP Q depletion-induced neurite complexity. Together, our results suggest that hnRNP Q1 may participate in localization of mRNAs encoding Cdc42 signaling factors in neurites, and thereby may regulate actin dynamics and control neuronal morphogenesis. PMID:22493061

  13. Neural crest development: the interplay between morphogenesis and cell differentiation.

    PubMed

    Erickson, C A; Reedy, M V

    1998-01-01

    The final pattern of tissues established during embryogenesis reflects the outcome of two developmental processes: differentiation and morphogenesis. Avian neural crest cells are an excellent system in which to study this interaction. In the first phase of neural crest cell migration, neural crest cells separate from the neural epithelium via an epithelial-mesenchymal transformation. We present three models to account for this process: (1) separation by asymmetric mitosis, (2) separation by generating tractional force in order to rupture cell adhesions and (3) loss of expression or function of cell-cell adhesion molecules that keep the presumptive neural crest cells tethered to the neural epithelium. Evidence is presented that the segregation of the neural crest lineage apart from the neural epithelium is caused by the epithelial-mesenchymal transformation. Once they have detached from the neural tube, neural crest cells take two pathways in the trunk of the chick embryo: (1) the ventral path between the neural tube and somite, where neural crest cells give rise to neurons and glial cells of the peripheral nervous systems, and (2) the dorsolateral path between the ectoderm and dermamyotome of the somite, where they differentiate into pigment cells of the skin. We present data to suggest that the migration and differentiation along the ventral path is controlled primarily by environmental cues, which we refer to as the environment-directed model of neural crest morphogenesis. Conversely, only melanoblasts can migrate into the dorsolateral space, and the ability to invade that path is dependent upon their early specification as melanoblasts. We call this the phenotype-directed model for neural crest cell migration and suggest that this latter model for the positioning of neural crest derivatives in the embryo may be more common than previously suspected. These observations invite a re-examination of patterning of other crest derivates, which previously were believed

  14. Laser microbeam manipulation of cell morphogenesis growing in fungal hyphae

    NASA Astrophysics Data System (ADS)

    Bracker, Charles E.; Murphy, Douglas J.; Lopez-Franco, Rosamaria

    1997-05-01

    Laser microbeam irradiation at 820 nm predictably and reproducibly altered morphogenetic patterns in fungal cells. Optical tweezers were highly effective as localized, noninvasive, and largely nondestructive probes under precise spatial and temporal control. In growing hyphae, the position of the Spitzenkorper (a multicomponent complex containing mainly secretory vesicles in the hyphal apex), is correlated with the site of maximum cell expansion during tip growth. The Spitzenkorper was not trapped by the laser, but moved away from the trap, and could be `chased' around the cell by the laser beam. Consequently, the direction of cell elongation was readily changed by moving the Spitzenkorper. When the laser was held steady at the cytoplasmic surface immediately beside the Spitzenkorper, an adventitious branch hypha was initiated on the same side of the hypha, suggesting that unilateral disturbance of vesicle traffic initiated a new lateral Spitzenkorper and hyphal branch near the original hyphal apex. If moving vesicles were trapped by the laser beam and transported to a different area of the cytoplasm near the cell surface, the cell profile bulged where the vesicles were newly concentrated. Variations in the mode of vesicle transfer caused: (1) single and multiple bulges, (2) adventitious branch hyphae, (3) increased cell diameter, and (4) changing directions of hyphal elongation. Thus, laser tweezers emerge as a powerful tool for controlling patterns of cell morphogenesis. The findings strongly support the hypothesis that sites of vesicle concentration and release to the cell surface are important determinants of cell morphogenesis in fungi. This conclusion lends support to the basic premises of a modern mathematical model of hyphal tip growth (the hyphoid/VSC model) but does not in itself provide the information needed for a comprehensive and integrated explanation of the mechanism of cell growth in fungi.

  15. [Morphogenesis and ultrastructure of basidiomycetes Agaricus and Pleurotus mitochondria].

    PubMed

    Matrosova, E V; Mazheĭka, I S; Kudriavtseva, O A; Kamzolkina, O V

    2009-01-01

    Mitochondrial morphogenesis in 31 strains of 9 species of Agaricus--A. arvensis Schaeff., A. bisporus (Lange) Imbach, A. bitorquis (Quel.) Sacc., A. campestris L., A. excellens (F. H. Moller) F. H. Moller, A. macrocarpus (F. H. Möller) F. H. Möller, A. silvaticus Schaeff., A. silvicola (Vittad.) Peck, A. xanthodermus Genev--and 2 strains of Pleurotus--P. ostreatus (Jacg.) P. Kumm., P. pulmonarius (Fr.) Quel.--has many common features in mitochondria distribution under favorable growth conditions (type 1) and in reconstruction of chondriom (fission or fragmentation) under unfavorable growth conditions and aging (type 2). The first type of mitochondria distribution was observed in heterokaryotic mycelium of some Agaricus strains and Pleurotus grown in agar medium during 7-14 days, and also in submerged mycelium of some Agaricus strains and Pleurotus. The second type of mitochondria distribution was observed in homokaryotic Agaricus strains under condition of starvation, in aging mycelium (28 days of growth), and in submerged mycelium of most of Agaricus strains. The first type of chondriom consists of small granular mitochondria in the apical cells and long snake-like network in subapical cells, and restores almost completely the mitochondrial network in the aging mycelium cells. The second type of chondriom consists of small granular mitochondria in all cells of mycelium. The surface of chondriom type 2 mitochondrial membrane was usually closely associated with ribosomes and changed crists. Such mycelium cells in A. bisporus strain Bs94 were TUNEL positive. So, the types of mitochondria morphogenesis in the Agaricus and Pleurotus mycelium cells are similar at different time and growth conditions and depend on complex of physiological and biochemical process in the mycelium cells.

  16. Jack vertebral dilator kyphoplasty for treatment of osteoporotic vertebral compression fractures.

    PubMed

    Li, Dapeng; Huang, Yonghui; Yang, Huilin; Chen, Qi; Sun, Taicun; Wu, Yan; Li, Xuefeng

    2014-01-01

    Osteoporotic vertebral compression fractures (OVCFs) are common in the elderly population and often involve the thoracolumbar vertebrae. Clinical symptoms of OVCFs include severe pain, loss of vertebral height, progressive kyphosis and increased mortality. Jack vertebral dilator kyphoplasty is a recently developed OVCFs treatment modality, with few systematic studies present in the literature. This retrospective study was designed to investigate the safety and efficacy of Jack vertebral dilator kyphoplasty for treating thoracolumbar OVCFs. Sixteen elderly patients (55-85 years) with solitary thoracolumbar OVCFs were treated with this procedure and followed-up (10-27 months). The amount of injected bone cement and operative time, preoperative and postoperative visual analogue scores, anterior and middle vertebral body heights, local kyphosis angle, and complications was analysed. The results showed that the method provided long-term pain relief and restoration of the vertebral body height and spinal alignment. No serious complications occurred, but two patients experienced recompression of the vertebral body, and one patient experienced cement leakage into a disc. In conclusion, Jack vertebral dilator kyphoplasty is a safe and effective minimally invasive procedure for treatment of OVCFs.

  17. Developmental mechanisms of vertebrate limb evolution.

    PubMed

    Cohn, M J

    2001-01-01

    Over the past few years, our understanding of the evolution of limbs has been improved by important new discoveries in the fossil record. Additionally, rapid progress has been made in identifying the molecular basis of vertebrate limb development. It is now possible to integrate these two areas of research in order to identify the molecular developmental mechanisms underlying the evolution of paired appendages in vertebrates. After the origin of paired appendages, several vertebrate lineages reduced or eliminated fins and limbs and returned to the limbless condition. Examples include eels, caecilians, snakes, slow worms and several marine mammals. Analyses of fossil and extant vertebrates show that evolution of limblessness frequently occurred together with elongation of the trunk and loss of clear morphological boundaries in the vertebral column. This may be suggestive of a common developmental mechanism linking these two processes. We have addressed this question by analysing python embryonic development at tissue, cellular and molecular levels, and we have identified a developmental mechanism which may account for evolution of limb loss in these animals.

  18. Developmental mechanisms of vertebrate limb evolution.

    PubMed

    Cohn, M J

    2001-01-01

    Over the past few years, our understanding of the evolution of limbs has been improved by important new discoveries in the fossil record. Additionally, rapid progress has been made in identifying the molecular basis of vertebrate limb development. It is now possible to integrate these two areas of research in order to identify the molecular developmental mechanisms underlying the evolution of paired appendages in vertebrates. After the origin of paired appendages, several vertebrate lineages reduced or eliminated fins and limbs and returned to the limbless condition. Examples include eels, caecilians, snakes, slow worms and several marine mammals. Analyses of fossil and extant vertebrates show that evolution of limblessness frequently occurred together with elongation of the trunk and loss of clear morphological boundaries in the vertebral column. This may be suggestive of a common developmental mechanism linking these two processes. We have addressed this question by analysing python embryonic development at tissue, cellular and molecular levels, and we have identified a developmental mechanism which may account for evolution of limb loss in these animals. PMID:11277086

  19. Wnt5a/Jnk and FGF/Mapk pathways regulate the cellular events shaping the vertebrate limb bud

    PubMed Central

    Gros, Jerome; Hu, Jimmy Kuang-Hsien; Vinegoni, Claudio; Feruglio, Paolo Fumene; Weissleder, Ralph; Tabin, Clifford J.

    2010-01-01

    SUMMARY The vertebrate limb is a classical model for understanding patterning of three-dimensional structures during embryonic development. While decades of research have elucidated the tissue and molecular interactions within the limb bud required for patterning and morphogenesis of the limb, the cellular and molecular events that shape the limb bud itself have remained largely unknown. We show that the mesenchymal cells of the early limb bud are not disorganized within the ectoderm as previously thought, but instead are highly organized and polarized. Using time lapse video microscopy we demonstrate that cells move and divide according to this orientation. The combination of oriented cell divisions and movements drives the proximal-to-distal elongation of the limb bud necessary to set the stage for subsequent patterning and morphogenesis. These cellular events are regulated by the combined activities of the Wnt and FGF pathways. We show that Wnt5a/JNK is necessary for the proper orientation of cell movements and cell division. In contrast FGF/Mapk signalling pathway, emanating from the AER, does not regulate cell orientation in the limb bud but instead establishes a gradient of cell velocity enabling continuous rearrangement of the cells at the distal tip of limb. PMID:21055947

  20. The vertebral column of Australopithecus sediba.

    PubMed

    Williams, Scott A; Ostrofsky, Kelly R; Frater, Nakita; Churchill, Steven E; Schmid, Peter; Berger, Lee R

    2013-04-12

    Two partial vertebral columns of Australopithecus sediba grant insight into aspects of early hominin spinal mobility, lumbar curvature, vertebral formula, and transitional vertebra position. Au. sediba likely possessed five non-rib-bearing lumbar vertebrae and five sacral elements, the same configuration that occurs modally in modern humans. This finding contrasts with other interpretations of early hominin regional vertebral numbers. Importantly, the transitional vertebra is distinct from and above the last rib-bearing vertebra in Au. sediba, resulting in a functionally longer lower back. This configuration, along with a strongly wedged last lumbar vertebra and other indicators of lordotic posture, would have contributed to a highly flexible spine that is derived compared with earlier members of the genus Australopithecus and similar to that of the Nariokotome Homo erectus skeleton.

  1. Hedgehog Secretion and Signal Transduction in Vertebrates

    PubMed Central

    Ryan, Kaitlyn E.; Chiang, Chin

    2012-01-01

    Signaling by the Hedgehog (Hh) family of secreted proteins is essential for proper embryonic patterning and development. Dysregulation of Hh signaling is associated with a variety of human diseases ranging from developmental disorders such as holoprosencephaly to certain forms of cancer, including medulloblastoma and basal cell carcinoma. Genetic studies in flies and mice have shaped our understanding of Hh signaling and revealed that nearly all core components of the pathway are highly conserved. Although many aspects of the Drosophila Hh pathway are conserved in vertebrates, mechanistic differences between the two species have begun to emerge. Perhaps the most striking divergence in vertebrate Hh signaling is its dependence on the primary cilium, a vestigial organelle that is largely absent in flies. This minireview will provide an overview of Hh signaling and present recent insights into vertebrate Hh secretion, receptor binding, and signal transduction. PMID:22474285

  2. [Amphioxus: how to become a vertebrate].

    PubMed

    Bertrand, Stéphanie; Camasses, Alain; Escriva, Hector

    2007-01-01

    Evo-devo is a young disciplin, which aims to explain the morphological evolution of organisms through developmental mechanisms and genes networks. A major question within this discipline is the origin of vertebrates. It seems now admitted that vertebrates derive from an invertebrate chordate ancestor. Several models among living chordate representatives are used today to answer this question. The small world of evo-evo interested in the emergence of vertebrates is ebullient about the advent of several totally sequenced genomes allowing comparative analyses to become evermore reliable. Furthermore "non classical" models are developed which can be submitted to refined developmental analysis. One of these is amphioxus (genus Branchyostoma), "a peaceful anchory fillet to illuminate chordate evolution" (Garcia-Fernandez, 2006a, b). The features of this model are described in this review.

  3. The vertebral column of Australopithecus sediba.

    PubMed

    Williams, Scott A; Ostrofsky, Kelly R; Frater, Nakita; Churchill, Steven E; Schmid, Peter; Berger, Lee R

    2013-04-12

    Two partial vertebral columns of Australopithecus sediba grant insight into aspects of early hominin spinal mobility, lumbar curvature, vertebral formula, and transitional vertebra position. Au. sediba likely possessed five non-rib-bearing lumbar vertebrae and five sacral elements, the same configuration that occurs modally in modern humans. This finding contrasts with other interpretations of early hominin regional vertebral numbers. Importantly, the transitional vertebra is distinct from and above the last rib-bearing vertebra in Au. sediba, resulting in a functionally longer lower back. This configuration, along with a strongly wedged last lumbar vertebra and other indicators of lordotic posture, would have contributed to a highly flexible spine that is derived compared with earlier members of the genus Australopithecus and similar to that of the Nariokotome Homo erectus skeleton. PMID:23580532

  4. Three Distinct Glutamate Decarboxylase Genes in Vertebrates

    PubMed Central

    Grone, Brian P.; Maruska, Karen P.

    2016-01-01

    Gamma-aminobutyric acid (GABA) is a widely conserved signaling molecule that in animals has been adapted as a neurotransmitter. GABA is synthesized from the amino acid glutamate by the action of glutamate decarboxylases (GADs). Two vertebrate genes, GAD1 and GAD2, encode distinct GAD proteins: GAD67 and GAD65, respectively. We have identified a third vertebrate GAD gene, GAD3. This gene is conserved in fishes as well as tetrapods. We analyzed protein sequence, gene structure, synteny, and phylogenetics to identify GAD3 as a homolog of GAD1 and GAD2. Interestingly, we found that GAD3 was lost in the hominid lineage. Because of the importance of GABA as a neurotransmitter, GAD3 may play important roles in vertebrate nervous systems. PMID:27461130

  5. The efficacy of radiotherapy for vertebral hemangiomas.

    PubMed

    Miszczyk, L; Ficek, K; Trela, K; Spindel, J

    2001-01-01

    Vertebral hemangiomas are benign, slowly growing tumors sometimes causing local pain in the spine and/or neurologic disorders. The present paper includes 14 cases of painful vertebral hemangiomas treated by radiotherapy. All patients were irradiated using standard fractionation scheme with a total dose 20-30 Gy. One month after the treatment complete pain relief was noted in 36% of cases, five months later in 67% of cases, but in the remaining cases partial pain relief was noted. No correlation between treatment outcome and different biological and technical factors was found. No dose-response relationship was noted. The results suggest that anti-inflamatory effect of radiation plays the major role in this kind of treatment and that radiotherapy for vertebral hemangiomas is easy, short and highly effective analgetic treatment modality.

  6. Cervical Vertebral Body Chordoma in a Cat.

    PubMed

    Hampel, R; Taylor-Brown, F; Priestnall, S L

    2016-05-01

    A 9-year-old, neutered female Maine Coon cat with a 6-week history of progressive ataxia was diagnosed with a cervical vertebral body mass using magnetic resonance imaging. The mass displaced and compressed the cervical spinal cord. The cat was humanely destroyed and necropsy examination confirmed a mass within the second cervical vertebral body. Microscopically, the mass was composed of large, clear, vacuolated ('physaliferous') cells. Immunohistochemically, the neoplastic cells expressed both cytokeratin and vimentin and the final diagnosis was a cervical, vertebral body chordoma. This is only the third report of a chordoma in this species and the first in this location. Chordoma should be considered as a potential differential diagnosis for tumours arising from the cervical vertebrae in the cat.

  7. Chitin is endogenously produced in vertebrates

    PubMed Central

    Sohn, Joel J.; Amemiya, Chris T.

    2015-01-01

    Chitin, a biopolymer of N-acetylglucosamine, is abundant in invertebrates and fungi, and is an important structural molecule. There has been a longstanding belief that vertebrates do not produce chitin, however, we have obtained compelling evidence to the contrary. Chitin synthase genes are present in numerous fishes and amphibians, and chitin is localized in situ to the lumen of the developing zebrafish gut, in epithelial cells of fish scales, and in at least three different cell types in larval salamander appendages. Chitin synthase gene knockdowns and various histochemical experiments in zebrafish further authenticated our results. Finally, a polysaccharide was extracted from scales of salmon that exhibited all the chemical hallmarks of chitin. Our data and analyses demonstrate the existence of endogenous chitin in vertebrates and suggest that it serves multiple roles in vertebrate biology. PMID:25772447

  8. AmphiFoxE4, an amphioxus winged helix/forkhead gene encoding a protein closely related to vertebrate thyroid transcription factor-2: expression during pharyngeal development

    NASA Technical Reports Server (NTRS)

    Yu, Jr-Kai; Holland, Linda Z.; Jamrich, Milan; Blitz, Ira L.; Hollan, Nicholas D.

    2002-01-01

    The full-length sequence and developmental expression of amphioxus AmphiFoxE4 are described. Transcripts of the gene are first detected in the pharyngeal endoderm, where the club-shaped gland is forming and subsequently in the definitive gland itself. AmphiFoxE4 is closely related to vertebrate genes encoding the thyroid-specific transcription factor-2 (TTF2), which plays an early developmental role in the morphogenesis of the thyroid gland and a later role in hormone-mediated control of thyroid function. In amphioxus, AmphiFoxE4 expression is not thyroid specific because the club-shaped gland, the only structure expressing the gene, is not homologous to the vertebrate thyroid; instead, the thyroid homologue of amphioxus is a specialized region of the pharyngeal endoderm called the endostyle. We propose that (a) the pharynx of an amphioxus-like ancestor of the vertebrates included a club-shaped gland that expressed FoxE4 as well as an endostyle that did not, and (b) the club-shaped gland soon disappeared in the vertebrate line of descent but (c) not before there was a homeogenetic transfer of FoxE4 expression from the club-shaped gland to the nearby endostyle. Such a transfer could have provided part of the genetic program enabling the endostyle to separate from the pharyngeal endoderm and migrate away as the rudiment of the thyroid gland.

  9. The evolution of early vertebrate photoreceptors.

    PubMed

    Collin, Shaun P; Davies, Wayne L; Hart, Nathan S; Hunt, David M

    2009-10-12

    Meeting the challenge of sampling an ancient aquatic landscape by the early vertebrates was crucial to their survival and would establish a retinal bauplan to be used by all subsequent vertebrate descendents. Image-forming eyes were under tremendous selection pressure and the ability to identify suitable prey and detect potential predators was thought to be one of the major drivers of speciation in the Early Cambrian. Based on the fossil record, we know that hagfishes, lampreys, holocephalans, elasmobranchs and lungfishes occupy critical stages in vertebrate evolution, having remained relatively unchanged over hundreds of millions of years. Now using extant representatives of these 'living fossils', we are able to piece together the evolution of vertebrate photoreception. While photoreception in hagfishes appears to be based on light detection and controlling circadian rhythms, rather than image formation, the photoreceptors of lampreys fall into five distinct classes and represent a critical stage in the dichotomy of rods and cones. At least four types of retinal cones sample the visual environment in lampreys mediating photopic (and potentially colour) vision, a sampling strategy retained by lungfishes, some modern teleosts, reptiles and birds. Trichromacy is retained in cartilaginous fishes (at least in batoids and holocephalans), where it is predicted that true scotopic (dim light) vision evolved in the common ancestor of all living gnathostomes. The capacity to discriminate colour and balance the tradeoff between resolution and sensitivity in the early vertebrates was an important driver of eye evolution, where many of the ocular features evolved were retained as vertebrates progressed on to land.

  10. Vertebral fractures in males with prolactinoma.

    PubMed

    Mazziotti, Gherardo; Porcelli, Teresa; Mormando, Marilda; De Menis, Ernesto; Bianchi, Antonio; Mejia, Carola; Mancini, Tatiana; De Marinis, Laura; Giustina, Andrea

    2011-06-01

    Data on osteoporotic fractures in hyperprolactinemia are limited. An increased prevalence of radiological vertebral fractures was recently observed in women with prolactin (PRL)-secreting adenoma, whereas it is unknown whether this observation may reflect a more general increased risk of fractures in this disease and whether the prevalence of fractures in males is affected by gonadal status. Thirty-two males (median age 47 years, range: 22-79) with PRL-secreting pituitary adenoma (10 with microadenoma and 22 with macroadenoma) and 64 control males, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 12 patients with PRL-secreting adenoma (37.5%) and in 5 controls (7.8%, P < 0.001). Fractured patients had lower BMD T-score (P = 0.007) and longer duration of disease (P < 0.001) as compared to patients who did not fracture. Fractures occurred more frequently (P = 0.03) in patients with untreated hyperprolactinemia versus patients treated with cabergoline whose frequency of vertebral fractures was still higher than control subjects. The prevalence of vertebral fractures was not significantly different between eugonadal and hypogonadal patients (33.3% vs. 38.5%; P = 0.8). Moreover, no significant (P = 0.4) difference in serum testosterone values was found between fractured and not fractured males. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in men with PRL-secreting adenoma. These findings would also suggest that PRL excess may produce negative skeletal effects independently of hypogonadism.

  11. Retinoids induce lumen morphogenesis in mammary epithelial cells.

    PubMed

    Montesano, Roberto; Soulié, Priscilla

    2002-12-01

    Lumen formation is a fundamental step in the development of the structural and functional units of glandular organs, such as alveoli and ducts. In an attempt to elucidate the molecular signals that govern this morphogenetic event, we set up an in vitro system in which cloned mammary epithelial cells grown in collagen gels under serum-free conditions form solid, lumen-less colonies. Addition of as little as 0.1% donor calf serum (DCS) was sufficient to induce the formation of a central cavity. Among a number of serum constituents analyzed, retinol was found to mimic the effect of DCS in inducing lumen morphogenesis. Since the biological activities of retinol are largely dependent on its conversion to all-trans-retinoic acid (RA), we examined in more detail the effect of RA on lumen formation. RA induced the formation of lumen-containing colonies (cysts) in a concentration- and time-dependent manner, a half-maximal effect after 9 days of culture being observed with 100 pM RA. The pleiotropic effects of retinoids are mediated by nuclear retinoic acid receptors (RARs; alpha, beta and gamma) and retinoid X receptors (RXRs; alpha, beta and gamma). To identify the signaling pathway involved in RA-induced lumen formation, we used receptor-specific synthetic retinoids. TTNPB, a selective RAR agonist, promoted lumen morphogenesis, whereas RXR-selective ligands lacked this activity. Lumen formation was also induced at picomolar concentrations by Am-580, a synthetic retinoid that selectively binds the RARalpha receptor subtype. Moreover, co-addition of Ro 41-5253, an antagonist of RARalpha, abrogated the lumen-inducing activity of both RA and DCS, indicating that this biological response is mediated through an RARalpha-dependent signaling pathway. To gain insight into the mechanisms underlying RA-induced lumen formation, we assessed the potential role of matrix metalloproteinases (MMP). Using gelatin zymography, we observed a dose-dependent increase in latent and active forms

  12. The evolution of vertebrate color vision.

    PubMed

    Jacobs, Gerald H

    2012-01-01

    Color vision is conventionally defined as the ability of animals to reliably discriminate among objects and lights based solely on differences in their spectral properties. Although the nature of color vision varies widely in different animals, a large majority of all vertebrate species possess some color vision and that fact attests to the adaptive importance this capacity holds as a tool for analyzing the environment. In recent years dramatic advances have been made in our understanding of the nature of vertebrate color vision and of the evolution of the biological mechanisms underlying this capacity. In this chapter I review and comment on these advances.

  13. Drosophila phosphopantothenoylcysteine synthetase is required for tissue morphogenesis during oogenesis

    PubMed Central

    Bosveld, Floris; Rana, Anil; Lemstra, Willy; Kampinga, Harm H; Sibon, Ody CM

    2008-01-01

    Background Coenzyme A (CoA) is an essential metabolite, synthesized from vitamin B5 by the subsequent action of five enzymes: PANK, PPCS, PPCDC, PPAT and DPCK. Mutations in Drosophila dPPCS disrupt female fecundity and in this study we analyzed the female sterile phenotype of dPPCS mutants in detail. Results We demonstrate that dPPCS is required for various processes that occur during oogenesis including chorion patterning. Our analysis demonstrates that a mutation in dPPCS disrupts the organization of the somatic and germ line cells, affects F-actin organization and results in abnormal PtdIns(4,5)P2 localization. Improper cell organization coincides with aberrant localization of the membrane molecules Gurken (Grk) and Notch, whose activities are required for specification of the follicle cells that pattern the eggshell. Mutations in dPPCS also induce alterations in scutellar patterning and cause wing vein abnormalities. Interestingly, mutations in dPANK and dPPAT-DPCK result in similar patterning defects. Conclusion Together, our results demonstrate that de novo CoA biosynthesis is required for proper tissue morphogenesis. PMID:18759961

  14. Whorl morphogenesis in the dasycladalean algae: the pattern formation viewpoint.

    PubMed Central

    Dumais, J; Harrison, L G

    2000-01-01

    The dasycladalean algae produce diverse whorled structures, among which the best known are the vegetative and reproductive whorls of Acetabularia acetabulum. In this paper, we review the literature pertaining to the origin of these structures. The question is addressed in terms of the necessary pattern-forming events and the possible mechanisms involved, an outlook we call the pattern formation viewpoint. The pattern-forming events involved in the morphogenesis of the vegetative and reproductive whorls of Acetabularia have been used to define five and six morphogenetic stages, respectively. We discuss three published mechanisms which account, at least in part, for the pattern-forming events. The mechanisms are mechanical buckling of the cell wall, reaction-diffusion of morphogen molecules along the cell membrane, and mechanochemical interactions between Ca2+ ions and the cytoskeleton in the cytosol. The numerous differences between these mechanisms provide experimental grounds to test their validity. To date, the results of these experiments point towards reaction diffusion as the most likely patterning mechanism. Finally, we consider the evolutionary origin of the vegetative and reproductive whorls and provide mechanistic explanations for some of the major evolutionary advances. PMID:10724462

  15. Formative cell divisions: principal determinants of plant morphogenesis.

    PubMed

    Smolarkiewicz, Michalina; Dhonukshe, Pankaj

    2013-03-01

    Formative cell divisions utilizing precise rotations of cell division planes generate and spatially place asymmetric daughters to produce different cell layers. Therefore, by shaping tissues and organs, formative cell divisions dictate multicellular morphogenesis. In animal formative cell divisions, the orientation of the mitotic spindle and cell division planes relies on intrinsic and extrinsic cortical polarity cues. Plants lack known key players from animals, and cell division planes are determined prior to the mitotic spindle stage. Therefore, it appears that plants have evolved specialized mechanisms to execute formative cell divisions. Despite their profound influence on plant architecture, molecular players and cellular mechanisms regulating formative divisions in plants are not well understood. This is because formative cell divisions in plants have been difficult to track owing to their submerged positions and imprecise timings of occurrence. However, by identifying a spatiotemporally inducible cell division plane switch system applicable for advanced microscopy techniques, recent studies have begun to uncover molecular modules and mechanisms for formative cell divisions. The identified molecular modules comprise developmentally triggered transcriptional cascades feeding onto microtubule regulators that now allow dissection of the hierarchy of the events at better spatiotemporal resolutions. Here, we survey the current advances in understanding of formative cell divisions in plants in the context of embryogenesis, stem cell functionality and post-embryonic organ formation.

  16. The Dynamics in Epithelial Cell Intercalation in Drosophila Morphogenesis

    NASA Astrophysics Data System (ADS)

    Wolf, Fred; Reichl, Lars; Kong, Deqing; Zhang, Yujun; Eule, Stephan; Metzger, Jakob; Großhans, Jörg

    2015-03-01

    Epithelial cell rearrangement is important for many processes in morphogenesis. During germband extension in early gastrulation of Drosophila embryos, exchange of neighbors is achieved by junction remodeling that follows a topological T1 process. Its first step is the constriction of dorsal-ventral junctions and fusion of two 3x vertices into a 4x vertex a process believed to be junction autonomous. We established a high throughput imaging pipeline, by which we recorded, segmented and analysed more than 1000 neighbor exchanges in drosophila embryos. Characterizing the dynamics of junction lengths we find that the constriction of cell contacts follows intriguingly simple quantitative laws. (1) The mean contact length decreases approximately as a square root of time to collapse. (2) The time dependent variance of contact lengths is proportional to the square of the mean. (3) The time dependent probability density of the contact lengths remains close to Gaussian during the entire process. These observations are sufficient to derive a stochastic differential equation for contact length that captures the non-equilibrium statistical mechanics of contact collapse. Supported by the German Research Foundation.

  17. The effect of fluorescent nanodiamonds on neuronal survival and morphogenesis

    NASA Astrophysics Data System (ADS)

    Huang, Yung-An; Kao, Chun-Wei; Liu, Kuang-Kai; Huang, Hou-Syun; Chiang, Ming-Han; Soo, Ching-Ren; Chang, Huan-Cheng; Chiu, Tzai-Wen; Chao, Jui-I.; Hwang, Eric

    2014-11-01

    Nanodiamond (ND) has emerged as a promising carbon nanomaterial for therapeutic applications. In previous studies, ND has been reported to have outstanding biocompatibility and high uptake rate in various cell types. ND containing nitrogen-vacancy centers exhibit fluorescence property is called fluorescent nanodiamond (FND), and has been applied for bio-labeling agent. However, the influence and application of FND on the nervous system remain elusive. In order to study the compatibility of FND on the nervous system, neurons treated with FNDs in vitro and in vivo were examined. FND did not induce cytotoxicity in primary neurons from either central (CNS) or peripheral nervous system (PNS); neither did intracranial injection of FND affect animal behavior. The neuronal uptake of FNDs was confirmed using flow cytometry and confocal microscopy. However, FND caused a concentration-dependent decrease in neurite length in both CNS and PNS neurons. Time-lapse live cell imaging showed that the reduction of neurite length was due to the spatial hindrance of FND on advancing axonal growth cone. These findings demonstrate that FNDs exhibit low neuronal toxicity but interfere with neuronal morphogenesis, and should be taken into consideration when applications involve actively growing neurites (e.g. nerve regeneration).

  18. Biochemical and Molecular Genetic Studies on Biosilica Morphogenesis in Diatoms

    NASA Astrophysics Data System (ADS)

    Kroger, N.; Poulsen, N.

    2006-12-01

    Diatoms are a large group of unicellular microalgae encased by silica cell walls that exhibit species-specific micro-and nanopatterns. Previously, we have characterized from diatoms unique phosphoproteins (termed silaffins) and unusually long polyamine chains (termed LCPA), which have both been implicated in biosilica formation. While the chemical structures of LCPA are largely conserved among different diatom species, the silaffins exhibit extensive structural variations. In vitro studies on the silica formation activities of silaffins and LCPA from the diatom Thalassiosira pseudonana indicate that silica morphogenesis is primarily determined by silaffins rather than LCPA. Recently, the complete genome sequence of T. pseudonana has become available, which for the first time opens the door to employ functional genomic approaches for studying the mechanism of silica biomineralization. To this end we have established the first genetic transformation system for T. pseudonana, which will be instrumental for analyzing the functions of silaffins in vivo, and for identifying new components of the diatom silica forming machinery. Here we describe the current knowledge on the structures and properties of silaffins and LCPA, the methods for genetic manipulation of T. pseudonana, and the first experimental steps towards functional genomics in diatoms.

  19. Mathematics and morphogenesis of cities: A geometrical approach

    NASA Astrophysics Data System (ADS)

    Courtat, Thomas; Gloaguen, Catherine; Douady, Stephane

    2011-03-01

    Cities are living organisms. They are out of equilibrium, open systems that never stop developing and sometimes die. The local geography can be compared to a shell constraining its development. In brief, a city’s current layout is a step in a running morphogenesis process. Thus cities display a huge diversity of shapes and none of the traditional models, from random graphs, complex networks theory, or stochastic geometry, takes into account the geometrical, functional, and dynamical aspects of a city in the same framework. We present here a global mathematical model dedicated to cities that permits describing, manipulating, and explaining cities’ overall shape and layout of their street systems. This street-based framework conciliates the topological and geometrical sides of the problem. From the static analysis of several French towns (topology of first and second order, anisotropy, streets scaling) we make the hypothesis that the development of a city follows a logic of division or extension of space. We propose a dynamical model that mimics this logic and that, from simple general rules and a few parameters, succeeds in generating a large diversity of cities and in reproducing the general features the static analysis has pointed out.

  20. Foamy Virus Protein—Nucleic Acid Interactions during Particle Morphogenesis

    PubMed Central

    Hamann, Martin V.; Lindemann, Dirk

    2016-01-01

    Compared with orthoretroviruses, our understanding of the molecular and cellular replication mechanism of foamy viruses (FVs), a subfamily of retroviruses, is less advanced. The FV replication cycle differs in several key aspects from orthoretroviruses, which leaves established retroviral models debatable for FVs. Here, we review the general aspect of the FV protein-nucleic acid interactions during virus morphogenesis. We provide a summary of the current knowledge of the FV genome structure and essential sequence motifs required for RNA encapsidation as well as Gag and Pol binding in combination with details about the Gag and Pol biosynthesis. This leads us to address open questions in FV RNA engagement, binding and packaging. Based on recent findings, we propose to shift the point of view from individual glycine-arginine-rich motifs having functions in RNA interactions towards envisioning the FV Gag C-terminus as a general RNA binding protein module. We encourage further investigating a potential new retroviral RNA packaging mechanism, which seems more complex in terms of the components that need to be gathered to form an infectious particle. Additional molecular insights into retroviral protein-nucleic acid interactions help us to develop safer, more specific and more efficient vectors in an era of booming genome engineering and gene therapy approaches. PMID:27589786

  1. The Extracellular Matrix In Development and Morphogenesis: A Dynamic View

    PubMed Central

    Rozario, Tania; DeSimone, Douglas W.

    2009-01-01

    The extracellular matrix (ECM) is synthesized and secreted by embryonic cells beginning at the earliest stages of development. Our understanding of ECM composition, structure and function has grown considerably in the last several decades and this knowledge has revealed that the extracellular microenvironment is critically important for cell growth, survival, differentiation and morphogenesis. ECM and the cellular receptors that interact with it mediate both physical linkages with the cytoskeleton and the bidirectional flow of information between the extracellular and intracellular compartments. This review considers the range of cell and tissue functions attributed to ECM molecules and summarizes recent findings specific to key developmental processes. The importance of ECM as a dynamic repository for growth factors is highlighted along with more recent studies implicating the 3-dimensional organization and physical properties of the ECM as it relates to cell signaling and the regulation of morphogenetic cell behaviors. Embryonic cell and tissue generated forces and mechanical signals arising from ECM adhesion represent emerging areas of interest in this field. PMID:19854168

  2. Early endocardial morphogenesis requires Scl/Tal1.

    PubMed

    Bussmann, Jeroen; Bakkers, Jeroen; Schulte-Merker, Stefan

    2007-08-01

    The primitive heart tube is composed of an outer myocardial and an inner endocardial layer that will give rise to the cardiac valves and septa. Specification and differentiation of these two cell layers are among the earliest events in heart development, but the embryonic origins and genetic regulation of early endocardial development remain largely undefined. We have analyzed early endocardial development in the zebrafish using time-lapse confocal microscopy and show that the endocardium seems to originate from a region in the lateral plate mesoderm that will give rise to hematopoietic cells of the primitive myeloid lineage. Endocardial precursors appear to rapidly migrate to the site of heart tube formation, where they arrive prior to the bilateral myocardial primordia. Analysis of a newly discovered zebrafish Scl/Tal1 mutant showed an additional and previously undescribed role of this transcription factor during the development of the endocardium. In Scl/Tal1 mutant embryos, endocardial precursors are specified, but migration is severely defective and endocardial cells aggregate at the ventricular pole of the heart. We further show that the initial fusion of the bilateral myocardial precursor populations occurs independently of the endocardium and tal1 function. Our results suggest early separation of the two components of the primitive heart tube and imply Scl/Tal1 as an indispensable component of the molecular hierarchy that controls endocardium morphogenesis.

  3. Endothelial cells regulate neural crest and second heart field morphogenesis

    PubMed Central

    Milgrom-Hoffman, Michal; Michailovici, Inbal; Ferrara, Napoleone; Zelzer, Elazar; Tzahor, Eldad

    2014-01-01

    ABSTRACT Cardiac and craniofacial developmental programs are intricately linked during early embryogenesis, which is also reflected by a high frequency of birth defects affecting both regions. The molecular nature of the crosstalk between mesoderm and neural crest progenitors and the involvement of endothelial cells within the cardio–craniofacial field are largely unclear. Here we show in the mouse that genetic ablation of vascular endothelial growth factor receptor 2 (Flk1) in the mesoderm results in early embryonic lethality, severe deformation of the cardio–craniofacial field, lack of endothelial cells and a poorly formed vascular system. We provide evidence that endothelial cells are required for migration and survival of cranial neural crest cells and consequently for the deployment of second heart field progenitors into the cardiac outflow tract. Insights into the molecular mechanisms reveal marked reduction in Transforming growth factor beta 1 (Tgfb1) along with changes in the extracellular matrix (ECM) composition. Our collective findings in both mouse and avian models suggest that endothelial cells coordinate cardio–craniofacial morphogenesis, in part via a conserved signaling circuit regulating ECM remodeling by Tgfb1. PMID:24996922

  4. Axin Regulates Dendritic Spine Morphogenesis through Cdc42-Dependent Signaling

    PubMed Central

    Chen, Yu; Liang, Zhuoyi; Fei, Erkang; Chen, Yuewen; Zhou, Xiaopu; Fang, Weiqun; Fu, Wing-Yu; Fu, Amy K. Y.; Ip, Nancy Y.

    2015-01-01

    During development, scaffold proteins serve as important platforms for orchestrating signaling complexes to transduce extracellular stimuli into intracellular responses that regulate dendritic spine morphology and function. Axin (“axis inhibitor”) is a key scaffold protein in canonical Wnt signaling that interacts with specific synaptic proteins. However, the cellular functions of these protein–protein interactions in dendritic spine morphology and synaptic regulation are unclear. Here, we report that Axin protein is enriched in synaptic fractions, colocalizes with the postsynaptic marker PSD-95 in cultured hippocampal neurons, and interacts with a signaling protein Ca2+/calmodulin-dependent protein kinase II (CaMKII) in synaptosomal fractions. Axin depletion by shRNA in cultured neurons or intact hippocampal CA1 regions significantly reduced dendritic spine density. Intriguingly, the defective dendritic spine morphogenesis in Axin-knockdown neurons could be restored by overexpression of the small Rho-GTPase Cdc42, whose activity is regulated by CaMKII. Moreover, pharmacological stabilization of Axin resulted in increased dendritic spine number and spontaneous neurotransmission, while Axin stabilization in hippocampal neurons reduced the elimination of dendritic spines. Taken together, our findings suggest that Axin promotes dendritic spine stabilization through Cdc42-dependent cytoskeletal reorganization. PMID:26204446

  5. Forces driving three-dimensional tissue patterning during morphogenesis

    NASA Astrophysics Data System (ADS)

    Lu, Heng; Sokolow, Adam; Tulu, U. Serdar; Kiehart, Daniel; Edwards, Glenn

    2012-02-01

    Dorsal closure is an essential stage of Drosophila embryogenesis and is a model system for in-vivo investigations of cell sheet morphogenesis. During closure a system of four biological processes work collectively to close a gap in the epithelium, which initially is filled with a transient tissue. The geometry of the dorsal opening is similar to that of two intersecting circular arcs being pulled apart at a nearly constant rate. Substantial progress in understanding the dynamics has been made in the past by largely viewing closure as a two-dimensional process. However, tissue and cell dynamics are not confined to the embryo surface. We have been investigating the three-dimensional kinematics of dorsal closure by imaging the actomyosin purse strings at the periphery of the dorsal opening and by imaging the apical belts of DE-cadherin in each cell within the opening. We have analyzed the results with the methods of analytic geometry. In addition, in the past we have determined the relative magnitudes of the forces that drive dorsal closure. We have been using magnetic tweezers, time-resolved in-vivo microscopy, and biophysical modeling to measure the net force and to determine the magnitude of each force.

  6. Extreme Morphogenesis and Ecological Specialization among Cretaceous Basal Ants.

    PubMed

    Perrichot, Vincent; Wang, Bo; Engel, Michael S

    2016-06-01

    Ants comprise one lineage of the triumvirate of eusocial insects and experienced their early diversification within the Cretaceous [1-9]. Their ecological success is generally attributed to their remarkable social behavior. Not all ants cooperate in social hunting, however, and some of the most effective predatory ants are solitary hunters with powerful trap jaws [10]. Recent evolutionary studies predict that the early branching lineages of extant ants formed small colonies of ground-dwelling, solitary specialist predators [2, 5, 7, 11, 12], while some Cretaceous fossils suggest group recruitment and socially advanced behavior among stem-group ants [9]. We describe a trap-jaw ant from 99 million-year-old Burmese amber with head structures that presumably functioned as a highly specialized trap for large-bodied prey. These are a cephalic horn resulting from an extreme modification of the clypeus hitherto unseen among living and extinct ants and scythe-like mandibles that extend high above the head, both demonstrating the presence of exaggerated morphogenesis early among stem-group ants. The new ant belongs to the Haidomyrmecini, possibly the earliest ant lineage [9], and together these trap-jaw ants suggest that at least some of the earliest Formicidae were solitary specialist predators. With their peculiar adaptations, haidomyrmecines had a refined ecology shortly following the advent of ants. PMID:27238278

  7. The green seaweed Ulva: a model system to study morphogenesis

    PubMed Central

    Wichard, Thomas; Charrier, Bénédicte; Mineur, Frédéric; Bothwell, John H.; Clerck, Olivier De; Coates, Juliet C.

    2015-01-01

    Green macroalgae, mostly represented by the Ulvophyceae, the main multicellular branch of the Chlorophyceae, constitute important primary producers of marine and brackish coastal ecosystems. Ulva or sea lettuce species are some of the most abundant representatives, being ubiquitous in coastal benthic communities around the world. Nonetheless the genus also remains largely understudied. This review highlights Ulva as an exciting novel model organism for studies of algal growth, development and morphogenesis as well as mutualistic interactions. The key reasons that Ulva is potentially such a good model system are: (i) patterns of Ulva development can drive ecologically important events, such as the increasing number of green tides observed worldwide as a result of eutrophication of coastal waters, (ii) Ulva growth is symbiotic, with proper development requiring close association with bacterial epiphytes, (iii) Ulva is extremely developmentally plastic, which can shed light on the transition from simple to complex multicellularity and (iv) Ulva will provide additional information about the evolution of the green lineage. PMID:25745427

  8. An extracellular adhesion molecule complex patterns dendritic branching and morphogenesis.

    PubMed

    Dong, Xintong; Liu, Oliver W; Howell, Audrey S; Shen, Kang

    2013-10-10

    Robust dendrite morphogenesis is a critical step in the development of reproducible neural circuits. However, little is known about the extracellular cues that pattern complex dendrite morphologies. In the model nematode Caenorhabditis elegans, the sensory neuron PVD establishes stereotypical, highly branched dendrite morphology. Here, we report the identification of a tripartite ligand-receptor complex of membrane adhesion molecules that is both necessary and sufficient to instruct spatially restricted growth and branching of PVD dendrites. The ligand complex SAX-7/L1CAM and MNR-1 function at defined locations in the surrounding hypodermal tissue, whereas DMA-1 acts as the cognate receptor on PVD. Mutations in this complex lead to dramatic defects in the formation, stabilization, and organization of the dendritic arbor. Ectopic expression of SAX-7 and MNR-1 generates a predictable, unnaturally patterned dendritic tree in a DMA-1-dependent manner. Both in vivo and in vitro experiments indicate that all three molecules are needed for interaction. PMID:24120131

  9. Quantification of embryonic atrioventricular valve biomechanics during morphogenesis

    PubMed Central

    Buskohl, Philip R.; Gould, Russell A.; Butcher, Jonathan T.

    2011-01-01

    Tissue assembly in the developing embryo is a rapid and complex process. While much research has focused on genetic regulatory machinery, understanding tissue level changes such as biomechanical remodeling remains a challenging experimental enigma. In the particular case of embryonic atrioventricular valves, micro-scale, amorphous cushions rapidly remodel into fibrous leaflets while simultaneously interacting with a demanding mechanical environment. In this study we employ two microscale mechanical measurement systems in conjunction with finite element analysis to quantify valve stiffening during valvulogenesis. The pipette aspiration technique is compared to a uniaxial load deformation, and the analytic expression for a uniaxially loaded bar is used to estimate the nonlinear material parameters of the experimental data. Effective modulus and strain energy density are analyzed as potential metrics for comparing mechanical stiffness. Avian atrioventricular valves from globular Hamburger–Hamilton stages HH25–HH34 were tested via the pipette method, while the planar HH36 leaflets were tested using the deformable post technique. Strain energy density between HH25 and HH34 septal leaflets increased 4.6±1.8 fold (±SD). The strain energy density of the HH36 septal leaflet was four orders of magnitude greater than the HH34 pipette result. Our results establish morphological thresholds for employing the micropipette aspiration and deformable post techniques for measuring uniaxial mechanical properties of embryonic tissues. Quantitative biomechanical analysis is an important and underserved complement to molecular and genetic experimentation of embryonic morphogenesis. PMID:22169154

  10. [Molecular mechanism of morphogenesis: a theory of locational DNA].

    PubMed

    Olovnikov, A M

    1996-11-01

    A molecular mechanism of reading of positional information by cells in morphogenesis and regeneration is proposed. It permits to translate the genome information into three-dimensional form of an organism. In the mechanism, a new fraction of DNA, so called "location DNA" is used which is suggested as a substitution instead of a former "egoistic" DNA. Domains, that are formed by this DNA and packed by lipid-containing bridges, are selectively unpacking in the gradient of inductor, the concentration of which positively correlates with the production of free radicals in the cells. Free radicals induce a selective destruction of lipid bridges which are variable in their resistance to the oxidative destruction. Hence the domains of location DNA are selectively decomactizing and activiting after bridge's elimination. In this way, a reading of positional information is performed. An epigenetic memory concerning the cellular determination state, that was already achieved, is based on the so called process of triplexation, the essence of which is a triplex formation, between signal RNA molecule and nascent double stranded DNA. A triplex is formed during the lagging strand synthesis or in the course of DNA repair synthesis. A telomeric element of postmitotic neurons, so called chronomere, assists to the organism in measuring of the flow of biological time, while chronomere length is an indicator of biological age of the organism.

  11. Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro.

    PubMed

    Nguyen, Duc-Huy T; Stapleton, Sarah C; Yang, Michael T; Cha, Susie S; Choi, Colin K; Galie, Peter A; Chen, Christopher S

    2013-04-23

    Angiogenesis is a complex morphogenetic process whereby endothelial cells from existing vessels invade as multicellular sprouts to form new vessels. Here, we have engineered a unique organotypic model of angiogenic sprouting and neovessel formation that originates from preformed artificial vessels fully encapsulated within a 3D extracellular matrix. Using this model, we screened the effects of angiogenic factors and identified two distinct cocktails that promoted robust multicellular endothelial sprouting. The angiogenic sprouts in our system exhibited hallmark structural features of in vivo angiogenesis, including directed invasion of leading cells that developed filopodia-like protrusions characteristic of tip cells, following stalk cells exhibiting apical-basal polarity, and lumens and branches connecting back to the parent vessels. Ultimately, sprouts bridged between preformed channels and formed perfusable neovessels. Using this model, we investigated the effects of angiogenic inhibitors on sprouting morphogenesis. Interestingly, the ability of VEGF receptor 2 inhibition to antagonize filopodia formation in tip cells was context-dependent, suggesting a mechanism by which vessels might be able to toggle between VEGF-dependent and VEGF-independent modes of angiogenesis. Like VEGF, sphingosine-1-phosphate also seemed to exert its proangiogenic effects by stimulating directional filopodial extension, whereas matrix metalloproteinase inhibitors prevented sprout extension but had no impact on filopodial formation. Together, these results demonstrate an in vitro 3D biomimetic model that reconstitutes the morphogenetic steps of angiogenic sprouting and highlight the potential utility of the model to elucidate the molecular mechanisms that coordinate the complex series of events involved in neovascularization. PMID:23569284

  12. Formative cell divisions: principal determinants of plant morphogenesis.

    PubMed

    Smolarkiewicz, Michalina; Dhonukshe, Pankaj

    2013-03-01

    Formative cell divisions utilizing precise rotations of cell division planes generate and spatially place asymmetric daughters to produce different cell layers. Therefore, by shaping tissues and organs, formative cell divisions dictate multicellular morphogenesis. In animal formative cell divisions, the orientation of the mitotic spindle and cell division planes relies on intrinsic and extrinsic cortical polarity cues. Plants lack known key players from animals, and cell division planes are determined prior to the mitotic spindle stage. Therefore, it appears that plants have evolved specialized mechanisms to execute formative cell divisions. Despite their profound influence on plant architecture, molecular players and cellular mechanisms regulating formative divisions in plants are not well understood. This is because formative cell divisions in plants have been difficult to track owing to their submerged positions and imprecise timings of occurrence. However, by identifying a spatiotemporally inducible cell division plane switch system applicable for advanced microscopy techniques, recent studies have begun to uncover molecular modules and mechanisms for formative cell divisions. The identified molecular modules comprise developmentally triggered transcriptional cascades feeding onto microtubule regulators that now allow dissection of the hierarchy of the events at better spatiotemporal resolutions. Here, we survey the current advances in understanding of formative cell divisions in plants in the context of embryogenesis, stem cell functionality and post-embryonic organ formation. PMID:23248201

  13. Morphogenesis of the Fission Yeast Cell through Cell Wall Expansion.

    PubMed

    Atilgan, Erdinc; Magidson, Valentin; Khodjakov, Alexey; Chang, Fred

    2015-08-17

    The shape of walled cells such as fungi, bacteria, and plants are determined by the cell wall. Models for cell morphogenesis postulate that the effects of turgor pressure and mechanical properties of the cell wall can explain the shapes of these diverse cell types. However, in general, these models await validation through quantitative experiments. Fission yeast Schizosaccharomyces pombe are rod-shaped cells that grow by tip extension and then divide medially through formation of a cell wall septum. Upon cell separation after cytokinesis, the new cell ends adopt a rounded morphology. Here, we show that this shape is generated by a very simple mechanical-based mechanism in which turgor pressure inflates the elastic cell wall in the absence of cell growth. This process is independent of actin and new cell wall synthesis. To model this morphological change, we first estimate the mechanical properties of the cell wall using several approaches. The lateral cell wall behaves as an isotropic elastic material with a Young's modulus of 50 ± 10 MPa inflated by a turgor pressure estimated to be 1.5 ± 0.2 MPa. Based upon these parameters, we develop a quantitative mechanical-based model for new end formation that reveals that the cell wall at the new end expands into its characteristic rounded shape in part because it is softer than the mature lateral wall. These studies provide a simple example of how turgor pressure expands the elastic cell wall to generate a particular cell shape.

  14. Single-cell analysis of endothelial morphogenesis in vivo

    PubMed Central

    Yu, Jianxin A.; Castranova, Daniel; Pham, Van N.; Weinstein, Brant M.

    2015-01-01

    Vessel formation has been extensively studied at the tissue level, but the difficulty in imaging the endothelium with cellular resolution has hampered study of the morphogenesis and behavior of endothelial cells (ECs) in vivo. We are using endothelial-specific transgenes and high-resolution imaging to examine single ECs in zebrafish. By generating mosaics with transgenes that simultaneously mark endothelial nuclei and membranes we are able to definitively identify and study the morphology and behavior of individual ECs during vessel sprouting and lumen formation. Using these methods, we show that developing trunk vessels are composed of ECs of varying morphology, and that single-cell analysis can be used to quantitate alterations in morphology and dynamics in ECs that are defective in proper guidance and patterning. Finally, we use single-cell analysis of intersegmental vessels undergoing lumen formation to demonstrate the coexistence of seamless transcellular lumens and single or multicellular enclosed lumens with autocellular or intercellular junctions, suggesting that heterogeneous mechanisms contribute to vascular lumen formation in vivo. The tools that we have developed for single EC analysis should facilitate further rigorous qualitative and quantitative analysis of EC morphology and behavior in vivo. PMID:26253401

  15. Whorl morphogenesis in the dasycladalean algae: the pattern formation viewpoint.

    PubMed

    Dumais, J; Harrison, L G

    2000-02-29

    The dasycladalean algae produce diverse whorled structures, among which the best known are the vegetative and reproductive whorls of Acetabularia acetabulum. In this paper, we review the literature pertaining to the origin of these structures. The question is addressed in terms of the necessary pattern-forming events and the possible mechanisms involved, an outlook we call the pattern formation viewpoint. The pattern-forming events involved in the morphogenesis of the vegetative and reproductive whorls of Acetabularia have been used to define five and six morphogenetic stages, respectively. We discuss three published mechanisms which account, at least in part, for the pattern-forming events. The mechanisms are mechanical buckling of the cell wall, reaction-diffusion of morphogen molecules along the cell membrane, and mechanochemical interactions between Ca2+ ions and the cytoskeleton in the cytosol. The numerous differences between these mechanisms provide experimental grounds to test their validity. To date, the results of these experiments point towards reaction diffusion as the most likely patterning mechanism. Finally, we consider the evolutionary origin of the vegetative and reproductive whorls and provide mechanistic explanations for some of the major evolutionary advances.

  16. Morphogenesis as a macroscopic self-organizing process.

    PubMed

    Beloussov, Lev V

    2012-09-01

    We start from reviewing different epistemological constructions used for explaining morphogenesis. Among them, we explore the explanatory power of a law-centered approach which includes top-down causation and the basic concepts of a self-organization theory. Within such a framework, we discuss the morphomechanical models based upon the presumption of feedbacks between mechanical stresses imposed onto a given embryo part from outside and those generated within the latter as a kind of active response. A number of elementary morphogenetic events demonstrating that these feedbacks are directed towards hyper-restoration (restoration with an overshoot) of the initial state of mechanical stresses are described. Moreover, we show that these reactions are bound together into the larger scale feedbacks. That permits to suggest a reconstruction of morphogenetic successions in early Metazoan development concentrated around two main archetypes distinguished by the blastopores geometry. The perspectives of applying the same approach to cell differentiation are outlined. By discussing the problem of positional information we suggest that the developmental pathway of a given embryo part depends upon its preceded deformations and the corresponding mechanical stresses rather than upon its static position at any moment of development. PMID:22609495

  17. Epidermal morphogenesis: the transcriptional program of human keratinocytes during stratification.

    PubMed

    Koria, Piyush; Andreadis, Stelios T

    2006-08-01

    The epidermis serves to protect the body against environmental assaults and at the same time is able to survive and replenish itself under harsh conditions. The epidermis accomplishes this feat via a well-orchestrated program of stratification and terminal differentiation that provides barrier against infection, radiation, and water loss. Despite significant progress in skin biology, many molecules and pathways that are involved in stratification and barrier formation remain unknown. Here, we employed tissue-engineered models of complete versus impaired epidermal stratification to discover the genes that may be important in this process. Transcriptional profiling at different stages of development showed significant differences in transcription, signaling, and most important metabolism-associated genes between fully stratified and poorly stratified epithelia. These transcriptional changes correlated well with functional data on cell proliferation, expression of adhesion molecules, and utilization of metabolic pathways, ultimately leading to different phenotypes. Our data identified genes that were not previously known to play a role in epidermis and established a link between metabolism and morphogenesis in skin epithelium.

  18. Reaction–diffusion model of hair-bundle morphogenesis

    PubMed Central

    Jacobo, Adrian; Hudspeth, A. J.

    2014-01-01

    The hair bundle, an apical specialization of the hair cell composed of several rows of regularly organized stereocilia and a kinocilium, is essential for mechanotransduction in the ear. Its precise organization allows the hair bundle to convert mechanical stimuli to electrical signals; mutations that alter the bundle’s morphology often cause deafness. However, little is known about the proteins involved in the process of morphogenesis and how the structure of the bundle arises through interactions between these molecules. We present a mathematical model based on simple reaction–diffusion mechanisms that can reproduce the shape and organization of the hair bundle. This model suggests that the boundary of the cell and the kinocilium act as signaling centers that establish the bundle’s shape. The interaction of two proteins forms a hexagonal Turing pattern—a periodic modulation of the concentrations of the morphogens, sustained by local activation and long-range inhibition of the reactants—that sets a blueprint for the location of the stereocilia. Finally we use this model to predict how different alterations to the system might impact the shape and organization of the hair bundle. PMID:25313064

  19. M-lattice: from morphogenesis to image processing.

    PubMed

    Sherstinsky, A S; Picard, R W

    1996-01-01

    The paper is based on reaction-diffusion, a nonlinear mechanism first proposed by Turing in 1952 to account for morphogenesis, the formation of shape and pattern in nature. One of the key limitations of reaction-diffusion systems is that they are generally unbounded, making them awkward for digital image processing. In this paper we introduce the "M-lattice", a system that preserves the pattern-formation properties of reaction-diffusion and is bounded. On the theoretical front, we establish how the M-lattice is closely related to the analog Hopfield network and the cellular neural network, but has more flexibility in how its variables interact. Like many "neurally inspired" systems, the bounded M-lattice also enables computer or analog VLSI implementations to simulate a variety of partial and ordinary differential equations. On the practical front, we demonstrate two novel applications of reaction-diffusion formulated as the new M-lattice. These are adaptive filtering, applied to the restoration and enhancement of fingerprint images, and nonlinear programming, applied to image halftoning in both "faithful" and "special effects" styles. PMID:18285202

  20. RhoA GTPase inhibition organizes contraction during epithelial morphogenesis.

    PubMed

    Mason, Frank M; Xie, Shicong; Vasquez, Claudia G; Tworoger, Michael; Martin, Adam C

    2016-08-29

    During morphogenesis, contraction of the actomyosin cytoskeleton within individual cells drives cell shape changes that fold tissues. Coordination of cytoskeletal contractility is mediated by regulating RhoA GTPase activity. Guanine nucleotide exchange factors (GEFs) activate and GTPase-activating proteins (GAPs) inhibit RhoA activity. Most studies of tissue folding, including apical constriction, have focused on how RhoA is activated by GEFs to promote cell contractility, with little investigation as to how GAPs may be important. Here, we identify a critical role for a RhoA GAP, Cumberland GAP (C-GAP), which coordinates with a RhoA GEF, RhoGEF2, to organize spatiotemporal contractility during Drosophila melanogaster apical constriction. C-GAP spatially restricts RhoA pathway activity to a central position in the apical cortex. RhoGEF2 pulses precede myosin, and C-GAP is required for pulsation, suggesting that contractile pulses result from RhoA activity cycling. Finally, C-GAP expression level influences the transition from reversible to irreversible cell shape change, which defines the onset of tissue shape change. Our data demonstrate that RhoA activity cycling and modulating the ratio of RhoGEF2 to C-GAP are required for tissue folding. PMID:27551058

  1. Foamy Virus Protein-Nucleic Acid Interactions during Particle Morphogenesis.

    PubMed

    Hamann, Martin V; Lindemann, Dirk

    2016-01-01

    Compared with orthoretroviruses, our understanding of the molecular and cellular replication mechanism of foamy viruses (FVs), a subfamily of retroviruses, is less advanced. The FV replication cycle differs in several key aspects from orthoretroviruses, which leaves established retroviral models debatable for FVs. Here, we review the general aspect of the FV protein-nucleic acid interactions during virus morphogenesis. We provide a summary of the current knowledge of the FV genome structure and essential sequence motifs required for RNA encapsidation as well as Gag and Pol binding in combination with details about the Gag and Pol biosynthesis. This leads us to address open questions in FV RNA engagement, binding and packaging. Based on recent findings, we propose to shift the point of view from individual glycine-arginine-rich motifs having functions in RNA interactions towards envisioning the FV Gag C-terminus as a general RNA binding protein module. We encourage further investigating a potential new retroviral RNA packaging mechanism, which seems more complex in terms of the components that need to be gathered to form an infectious particle. Additional molecular insights into retroviral protein-nucleic acid interactions help us to develop safer, more specific and more efficient vectors in an era of booming genome engineering and gene therapy approaches. PMID:27589786

  2. Transposon-mediated Genome Manipulations in Vertebrates

    PubMed Central

    Ivics, Zoltán; Li, Meng Amy; Mátés, Lajos; Boeke, Jef D.; Bradley, Allan; Izsvák, Zsuzsanna

    2010-01-01

    Transposable elements are segments of DNA with the unique ability to move about in the genome. This inherent feature can be exploited to harness these elements as gene vectors for diverse genome manipulations. Transposon-based genetic strategies have been established in vertebrate species over the last decade, and current progress in this field indicates that transposable elements will serve as indispensable tools in the genetic toolkit of vertebrate models. In particular, transposons can be applied as vectors for somatic and germline transgenesis, and as insertional mutagens in both loss-of-function and gain-of-function forward mutagenesis screens. The major advantage of using transposons as genetic tools is that they facilitate analysis of gene function in an easy, controlled and scalable manner. Transposon-based technologies are beginning to be exploited to link sequence information to gene functions in vertebrate models. In this article, we provide an overview of transposon-based methods used in vertebrate model organisms, and highlight the most important considerations concerning genetic applications of the transposon systems. PMID:19478801

  3. Vertebral choristoma in lipomyelomeningocele: a case report.

    PubMed

    Joshua, S P; Singh, Pankaj Kumar; Mahapatra, A K

    2012-01-01

    Lipomeningocele is a type of occult spinal dysraphism characterized by a subcutaneous lipomatous mass that protrudes through a midline bony defect. We report a rare presentation of this condition--a vertebral choristoma wherein the lipomatous mass displaced the normally formed posterior elements--lamina and spinous process of L4 vertebra dorsally to an abnormal location in the absence of a bony defect.

  4. Vertebral osteomyelitis due to Staphylococcus lugdunensis.

    PubMed Central

    Murdoch, D R; Everts, R J; Chambers, S T; Cowan, I A

    1996-01-01

    We present the first reported case of vertebral osteomyelitis due to Staphylococcus lugdunensis. The infection occurred in an 80-year-old woman who had been taking glucocorticosteroids. S. lugdunensis is a coagulase-negative staphylococcus with considerable potential as a human pathogen. Isolation of this organism should be regarded as significant unless evidence suggests otherwise. PMID:8815128

  5. [Sex inversion and epigenetic regulation in Vertebrates].

    PubMed

    Trukhina, A V; Lukina, N A; Nekrasova, A A; Smirnov, A F

    2015-03-01

    This review discusses issues related to the regulation of sex determination and differentiation in various groups of Vertebrates. Special attention was paid to factors of external and internal control for various genetic systems of sex determination, as well as to the epigenetic control of this process. Opportunities for sex inversion in various animals were also discussed.

  6. Diagnosis and Management of Vertebral Compression Fractures.

    PubMed

    McCarthy, Jason; Davis, Amy

    2016-07-01

    Vertebral compression fractures (VCFs) are the most common complication of osteoporosis, affecting more than 700,000 Americans annually. Fracture risk increases with age, with four in 10 white women older than 50 years experiencing a hip, spine, or vertebral fracture in their lifetime. VCFs can lead to chronic pain, disfigurement, height loss, impaired activities of daily living, increased risk of pressure sores, pneumonia, and psychological distress. Patients with an acute VCF may report abrupt onset of back pain with position changes, coughing, sneezing, or lifting. Physical examination findings are often normal, but can demonstrate kyphosis and midline spine tenderness. More than two-thirds of patients are asymptomatic and diagnosed incidentally on plain radiography. Acute VCFs may be treated with analgesics such as acetaminophen, nonsteroidal anti-inflammatory drugs, narcotics, and calcitonin. Physicians must be mindful of medication adverse effects in older patients. Other conservative therapeutic options include limited bed rest, bracing, physical therapy, nerve root blocks, and epidural injections. Percutaneous vertebral augmentation, including vertebroplasty and kyphoplasty, is controversial, but can be considered in patients with inadequate pain relief with nonsurgical care or when persistent pain substantially affects quality of life. Family physicians can help prevent vertebral fractures through management of risk factors and the treatment of osteoporosis. PMID:27386723

  7. Pleistocene vertebrates of the Yukon Territory

    NASA Astrophysics Data System (ADS)

    Harington, C. R.

    2011-08-01

    Unglaciated parts of the Yukon constitute one of the most important areas in North America for yielding Pleistocene vertebrate fossils. Nearly 30 vertebrate faunal localities are reviewed spanning a period of about 1.6 Ma (million years ago) to the close of the Pleistocene some 10 000 BP (radiocarbon years before present, taken as 1950). The vertebrate fossils represent at least 8 species of fishes, 1 amphibian, 41 species of birds and 83 species of mammals. Dominant among the large mammals are: steppe bison ( Bison priscus), horse ( Equus sp.), woolly mammoth ( Mammuthus primigenius), and caribou ( Rangifer tarandus) - signature species of the Mammoth Steppe fauna ( Fig. 1), which was widespread from the British Isles, through northern Europe, and Siberia to Alaska, Yukon and adjacent Northwest Territories. The Yukon faunas extend from Herschel Island in the north to Revenue Creek in the south and from the Alaskan border in the west to Ketza River in the east. The Yukon holds evidence of the earliest-known people in North America. Artifacts made from bison, mammoth and caribou bones from Bluefish Caves, Old Crow Basin and Dawson City areas show that people had a substantial knowledge of making and using bone tools at least by 25 000 BP, and possibly as early as 40 000 BP. A suggested chronological sequence of Yukon Pleistocene vertebrates ( Table 1) facilitates comparison of selected faunas and indicates the known duration of various taxa.

  8. Control of Vertebrate Pests of Agricultural Crops.

    ERIC Educational Resources Information Center

    Wingard, Robert G.; Studholme, Clinton R.

    This agriculture extension service publication of Pennsylvania State University discusses the damage from and control of vertebrate pests. Specific discussions describe the habits, habitat, and various control measures for blackbirds and crows, deer, meadow and pine mice, European starlings, and woodchucks. Where confusion with non-harmful species…

  9. A Cambrian origin for vertebrate rods

    PubMed Central

    Asteriti, Sabrina; Grillner, Sten; Cangiano, Lorenzo

    2015-01-01

    Vertebrates acquired dim-light vision when an ancestral cone evolved into the rod photoreceptor at an unknown stage preceding the last common ancestor of extant jawed vertebrates (∼420 million years ago Ma). The jawless lampreys provide a unique opportunity to constrain the timing of this advance, as their line diverged ∼505 Ma and later displayed high-morphological stability. We recorded with patch electrodes the inner segment photovoltages and with suction electrodes the outer segment photocurrents of Lampetra fluviatilis retinal photoreceptors. Several key functional features of jawed vertebrate rods are present in their phylogenetically homologous photoreceptors in lamprey: crucially, the efficient amplification of the effect of single photons, measured by multiple parameters, and the flow of rod signals into cones. These results make convergent evolution in the jawless and jawed vertebrate lines unlikely and indicate an early origin of rods, implying strong selective pressure toward dim-light vision in Cambrian ecosystems. DOI: http://dx.doi.org/10.7554/eLife.07166.001 PMID:26095697

  10. A comparative analysis of vertebrate sex determination.

    PubMed

    Sinclair, Andrew; Smith, Craig; Western, Patrick; McClive, Peter

    2002-01-01

    Sex determination in vertebrates is controlled by a variety of mechanisms. We compared the expression of SF1, DAX1, DMRT1, SOX9 and AMH during gonadogenesis in the mouse, chicken and alligator embryo. In contrast to the expression profile of Sf1 in mouse embryos, chicken and alligator embryos show higher levels of Sf1 expression in the developing ovaries compared to testes. This may reflect the higher level of sex hormone synthesis in the ovary compared to the testis in chickens and alligators. The DAX1 gene has a similar expression profile in all three vertebrate species but appears to have different gene structure. As in mouse, DMRT1 was expressed at very high levels in the chicken and alligator male gonad. The male-specific up-regulation of SOX9 expression appears to be a common feature in all three vertebrates. In the chicken and alligator AMH is expressed prior to SOX9, suggesting that in these species SOX9 cannot initiate AMH expression as it does in mammals. SOX9 acts at multiple points in the vertebrate testis pathway but it appears that only some of these functions have been conserved through evolution. PMID:11990786

  11. Vertebrate Pest Control. Sale Publication 4077.

    ERIC Educational Resources Information Center

    Stimmann, M. W.; Clark, Dell O.

    This guide gives descriptions of common vertebrate pests and guidelines for using some common pesticides. The pests discussed are rats, mice, bats, moles, muskrats, ground squirrels, and gophers. Information is given for each pest on the type of damage the pest can do, the habitat and biology of the pest, and the most effective control methods.…

  12. Pattern and morphogenesis of presumptive superficial mesoderm in two closely related species, Xenopus laevis and Xenopus tropicalis.

    PubMed

    Shook, David R; Majer, Christina; Keller, Ray

    2004-06-01

    The mesoderm, comprising the tissues that come to lie entirely in the deep layer, originates in both the superficial epithelial and the deep mesenchymal layers of the early amphibian embryo. Here, we characterize the mechanisms by which the superficial component of the presumptive mesoderm ingresses into the underlying deep mesenchymal layer in Xenopus tropicalis and extend our previous findings for Xenopus laevis. Fate mapping the superficial epithelium of pregastrula stage embryos demonstrates ingression of surface cells into both paraxial and axial mesoderm (including hypochord), in similar patterns and amounts in both species. Superficial presumptive notochord lies medially, flanked by presumptive hypochord and both overlie the deep region of the presumptive notochord. These tissues are flanked laterally by superficial presumptive somitic mesoderm, the anterior tip of which also appears to overlay the presumptive deep notochord. Time-lapse recordings show that presumptive somitic and notochordal cells move out of the roof of the gastrocoel and into the deep region during neurulation, whereas hypochordal cells ingress after neurulation. Scanning electron microscopy at the stage and position where ingression occurs suggests that superficial presumptive somitic cells in X. laevis ingress into the deep region as bottle cells whereas those in X. tropicalis ingress by "relamination" (e.g., [Dev. Biol. 174 (1996) 92]). In both species, the superficially derived presumptive somitic cells come to lie in the medial region of the presumptive somites during neurulation. By the early tailbud stages, these cells lie at the horizontal myoseptum of the somites. The morphogenic pathway of these cells strongly resembles that of the primary slow muscle pioneer cells of the zebrafish. We present a revised fate map of Xenopus, and we discuss the conservation of superficial mesoderm within amphibians and across the chordates and its implications for the role of this tissue in

  13. [Gas dissection of the vertebral body or the vertebral intrasomatic space phenomenon. Physiopathological arguments].

    PubMed

    Michel, J L; Bouzat, J; Rivoal, A; de Pradel de Lamaze, P; Viallet, J F; Belin, J; Merle, P

    1982-01-01

    Some features concerning the ischemic origin of the gaseous dissection of the vertebral body and the physiopathology of the necrose, are considered in the adult: --in the way, the anterior topography of vaccum phenomenon is on the model of the arterial distribution in the vertebral body, implying ischemic origin of gaseous dissection; --further, two cases of intravertebral vaccum cleft, noticed after minor trauma, suggest the major role of fractures at the origin of ischemia.

  14. Vertebral body stenting: a new method for vertebral augmentation versus kyphoplasty

    PubMed Central

    Martin, Heiner; Fuerderer, Sebastian; Gabl, Michael; Roeder, Christoph; Heini, Paul; Mittlmeier, Thomas

    2010-01-01

    Vertebroplasty and kyphoplasty are well-established minimally invasive treatment options for compression fractures of osteoporotic vertebral bodies. Possible procedural disadvantages, however, include incomplete fracture reduction or a significant loss of reduction after balloon tamp deflation, prior to cement injection. A new procedure called “vertebral body stenting” (VBS) was tested in vitro and compared to kyphoplasty. VBS uses a specially designed catheter-mounted stent which can be implanted and expanded inside the vertebral body. As much as 24 fresh frozen human cadaveric vertebral bodies (T11-L5) were utilized. After creating typical compression fractures, the vertebral bodies were reduced by kyphoplasty (n = 12) or by VBS (n = 12) and then stabilized with PMMA bone cement. Each step of the procedure was performed under fluoroscopic control and analysed quantitatively. Finally, static and dynamic biomechanical tests were performed. A complete initial reduction of the fractured vertebral body height was achieved by both systems. There was a significant loss of reduction after balloon deflation in kyphoplasty compared to VBS, and a significant total height gain by VBS (mean ± SD in %, p < 0.05, demonstrated by: anterior height loss after deflation in relation to preoperative height [kyphoplasty: 11.7 ± 6.2; VBS: 3.7 ± 3.8], and total anterior height gain [kyphoplasty: 8.0 ± 9.4; VBS: 13.3 ± 7.6]). Biomechanical tests showed no significant stiffness and failure load differences between systems. VBS is an innovative technique which allows for the possibly complete reduction of vertebral compression fractures and helps maintain the restored height by means of a stent. The height loss after balloon deflation is significantly decreased by using VBS compared to kyphoplasty, thus offering a new promising option for vertebral augmentation. PMID:20191393

  15. Determination of vertebral pose in 3D by minimization of vertebral asymmetry

    NASA Astrophysics Data System (ADS)

    Vrtovec, Tomaž; Pernuš, Franjo; Likar, Boštjan

    2011-03-01

    The vertebral pose in three dimensions (3D) may provide valuable information for quantitative clinical measurements or aid the initialization of image analysis techniques. We propose a method for automated determination of the vertebral pose in 3D that, in an iterative registration scheme, estimates the position and rotation of the vertebral coordinate system in 3D images. By searching for the hypothetical points, which are located where the boundaries of anatomical structures would have maximal symmetrical correspondences when mirrored over the vertebral planes, the asymmetry of vertebral anatomical structures is minimized. The method was evaluated on 14 normal and 14 scoliotic vertebrae in images acquired by computed tomography (CT). For each vertebra, 1000 randomly initialized experiments were performed. The results show that the vertebral pose can be successfully determined in 3D with mean accuracy of 0.5mm and 0.6° and mean precision of 0.17mm and 0.17. according to the 3D position and 3D rotation, respectively.

  16. Constitutive Expresser of Pathogenesis Related Genes 1 Is Required for Pavement Cell Morphogenesis in Arabidopsis.

    PubMed

    Han, Bing; Chen, Liang; Wang, Jing; Wu, Zhongliang; Yan, Longfeng; Hou, Suiwen

    2015-01-01

    For over 50 years, researchers have focused on the mechanisms underlying the important roles of the cytoskeleton in controlling the cell growth direction and cell expansion. In our study, we performed ethyl methane sulfonate mutagenesis on Col-0 background and identified two new CONSTITUTIVE EXPRESSER OF PATHOGENESIS RELATED GENES 1 (CPR1) alleles with pavement cell (PC) morphogenetic defects. Morphological characterizations showed that polar growth initiation and expansion of PCs are seriously suppressed in cpr1. Closer cytoskeleton investigation showed that the directional arrangement of microtubules (MTs) during PC development is defective and the cortical fine actin filaments cannot be aggregated effectively to form actin cable networks in cpr1 mutants. These results suggest that the abnormal PC morphogenesis in cpr1 is accompanying with the aberrant arrangement of cytoskeleton. Site-directed mutagenesis and knockout within the F-box-associated (FBA) domain, which is reported to be a motif for recognizing particular substrates of CPR1, proved that the FBA domain is indispensable for normal CPR1 regulation of the PC morphogenesis. Further genetic analysis indicated that the defects on PC morphogenesis of cpr1 depend on two lipase-like proteins, ENHANCED DISEASE SUSCEPTIBILITY 1 and PHYTOALEXIN DEFICIENT 4. Our results provide further insights into the relationship between the cytoskeleton and PC morphogenesis, and suggest that the cytoskeleton-mediated PC morphogenesis control might be tightly linked to plant defense responses. PMID:26193674

  17. Conserved RNA-Binding Proteins Required for Dendrite Morphogenesis in Caenorhabditis elegans Sensory Neurons

    PubMed Central

    Antonacci, Simona; Forand, Daniel; Wolf, Margaret; Tyus, Courtney; Barney, Julia; Kellogg, Leah; Simon, Margo A.; Kerr, Genevieve; Wells, Kristen L.; Younes, Serena; Mortimer, Nathan T.; Olesnicky, Eugenia C.; Killian, Darrell J.

    2015-01-01

    The regulation of dendritic branching is critical for sensory reception, cell−cell communication within the nervous system, learning, memory, and behavior. Defects in dendrite morphology are associated with several neurologic disorders; thus, an understanding of the molecular mechanisms that govern dendrite morphogenesis is important. Recent investigations of dendrite morphogenesis have highlighted the importance of gene regulation at the posttranscriptional level. Because RNA-binding proteins mediate many posttranscriptional mechanisms, we decided to investigate the extent to which conserved RNA-binding proteins contribute to dendrite morphogenesis across phyla. Here we identify a core set of RNA-binding proteins that are important for dendrite morphogenesis in the PVD multidendritic sensory neuron in Caenorhabditis elegans. Homologs of each of these genes were previously identified as important in the Drosophila melanogaster dendritic arborization sensory neurons. Our results suggest that RNA processing, mRNA localization, mRNA stability, and translational control are all important mechanisms that contribute to dendrite morphogenesis, and we present a conserved set of RNA-binding proteins that regulate these processes in diverse animal species. Furthermore, homologs of these genes are expressed in the human brain, suggesting that these RNA-binding proteins are candidate regulators of dendrite development in humans. PMID:25673135

  18. Constitutive Expresser of Pathogenesis Related Genes 1 Is Required for Pavement Cell Morphogenesis in Arabidopsis.

    PubMed

    Han, Bing; Chen, Liang; Wang, Jing; Wu, Zhongliang; Yan, Longfeng; Hou, Suiwen

    2015-01-01

    For over 50 years, researchers have focused on the mechanisms underlying the important roles of the cytoskeleton in controlling the cell growth direction and cell expansion. In our study, we performed ethyl methane sulfonate mutagenesis on Col-0 background and identified two new CONSTITUTIVE EXPRESSER OF PATHOGENESIS RELATED GENES 1 (CPR1) alleles with pavement cell (PC) morphogenetic defects. Morphological characterizations showed that polar growth initiation and expansion of PCs are seriously suppressed in cpr1. Closer cytoskeleton investigation showed that the directional arrangement of microtubules (MTs) during PC development is defective and the cortical fine actin filaments cannot be aggregated effectively to form actin cable networks in cpr1 mutants. These results suggest that the abnormal PC morphogenesis in cpr1 is accompanying with the aberrant arrangement of cytoskeleton. Site-directed mutagenesis and knockout within the F-box-associated (FBA) domain, which is reported to be a motif for recognizing particular substrates of CPR1, proved that the FBA domain is indispensable for normal CPR1 regulation of the PC morphogenesis. Further genetic analysis indicated that the defects on PC morphogenesis of cpr1 depend on two lipase-like proteins, ENHANCED DISEASE SUSCEPTIBILITY 1 and PHYTOALEXIN DEFICIENT 4. Our results provide further insights into the relationship between the cytoskeleton and PC morphogenesis, and suggest that the cytoskeleton-mediated PC morphogenesis control might be tightly linked to plant defense responses.

  19. Hedgehog signalling controls zebrafish neural keel morphogenesis via its level-dependent effects on neurogenesis.

    PubMed

    Takamiya, Masanari; Campos-Ortega, Jose A

    2006-04-01

    We investigated the role of hedgehog (Hh) signalling on zebrafish neurulation, focusing on the intimate relationship between neurogenesis and morphogenesis during the neural keel stage. Through the analyses of Hh loss- and gain-of-function phenotypes, we found that Hh signalling controls the neural keel morphogenesis. To investigate underlying mechanisms, we examined cellular elongation polarity in the neural keel of Hh loss- and gain-of-function phenotypes and compared this with the deficient phenotype of a planar cell polarity (PCP) molecule, Trilobite/Strabismus. We found that Hh signalling controls cell elongation polarity of the neuroepithelium at least in part by means of PCP pathway; however, its effects are not strong enough per se to affect keel morphogenesis; instead Hh signalling mainly controls keel morphogenesis by means of affecting both medial and lateral neurogenesis. We devised a method for precise evaluation of neurogenesis in loss- and gain-of-Hh phenotypes that compensates for its delay caused by disturbed morphogenesis. We present a model that Hh signalling exerts level-dependent and binary-opposite effects on medial neurogenesis, whose modification to explain lateral neurogenesis reveals regional differences of underlying mechanisms between the two proneural domains. Such differences seem to be created in part by regional effector signalling; the effects of high Hh-signalling on medial neurogenesis can be reversed in accordance to medial Tri/Stbm level, in a polarity independent manner.

  20. Melatonin Inhibits Embryonic Salivary Gland Branching Morphogenesis by Regulating Both Epithelial Cell Adhesion and Morphology

    PubMed Central

    Miura, Jiro; Sakai, Manabu; Uchida, Hitoshi; Nakamura, Wataru; Nohara, Kanji; Maruyama, Yusuke; Hattori, Atsuhiko; Sakai, Takayoshi

    2015-01-01

    Many organs, including salivary glands, lung, and kidney, are formed by epithelial branching during embryonic development. Branching morphogenesis occurs via either local outgrowths or the formation of clefts that subdivide epithelia into buds. This process is promoted by various factors, but the mechanism of branching morphogenesis is not fully understood. Here we have defined melatonin as a potential negative regulator or “brake” of branching morphogenesis, shown that the levels of it and its receptors decline when branching morphogenesis begins, and identified the process that it regulates. Melatonin has various physiological functions, including circadian rhythm regulation, free-radical scavenging, and gonadal development. Furthermore, melatonin is present in saliva and may have an important physiological role in the oral cavity. In this study, we found that the melatonin receptor is highly expressed on the acinar epithelium of the embryonic submandibular gland. We also found that exogenous melatonin reduces salivary gland size and inhibits branching morphogenesis. We suggest that this inhibition does not depend on changes in either proliferation or apoptosis, but rather relates to changes in epithelial cell adhesion and morphology. In summary, we have demonstrated a novel function of melatonin in organ formation during embryonic development. PMID:25876057

  1. Morphogenesis of the C. elegans Intestine Involves Axon Guidance Genes.

    PubMed

    Asan, Alparsan; Raiders, Stephan A; Priess, James R

    2016-04-01

    Genetic and molecular studies have provided considerable insight into how various tissue progenitors are specified in early embryogenesis, but much less is known about how those progenitors create three-dimensional tissues and organs. The C. elegans intestine provides a simple system for studying how a single progenitor, the E blastomere, builds an epithelial tube of 20 cells. As the E descendants divide, they form a primordium that transitions between different shapes over time. We used cell contours, traced from confocal optical z-stacks, to build a 3D graphic reconstruction of intestine development. The reconstruction revealed several new aspects of morphogenesis that extend and clarify previous observations. The first 8 E descendants form a plane of four right cells and four left cells; the plane arises through oriented cell divisions and VANG-1/Van Gogh-dependent repositioning of any non-planar cells. LIN-12/Notch signaling affects the left cells in the E8 primordium, and initiates later asymmetry in cell packing. The next few stages involve cell repositioning and intercalation events that shuttle cells to their final positions, like shifting blocks in a Rubik's cube. Repositioning involves breaking and replacing specific adhesive contacts, and some of these events involve EFN-4/Ephrin, MAB-20/semaphorin-2a, and SAX-3/Robo. Once cells in the primordium align along a common axis and in the correct order, cells at the anterior end rotate clockwise around the axis of the intestine. The anterior rotation appears to align segments of the developing lumen into a continuous structure, and requires the secreted ligand UNC-6/netrin, the receptor UNC-40/DCC, and an interacting protein called MADD-2. Previous studies showed that rotation requires a second round of LIN-12/Notch signaling in cells on the right side of the primordium, and we show that MADD-2-GFP appears to be downregulated in those cells. PMID:27035721

  2. Molecular basis of cell integrity and morphogenesis in Saccharomyces cerevisiae.

    PubMed Central

    Cid, V J; Durán, A; del Rey, F; Snyder, M P; Nombela, C; Sánchez, M

    1995-01-01

    In fungi and many other organisms, a thick outer cell wall is responsible for determining the shape of the cell and for maintaining its integrity. The budding yeast Saccharomyces cerevisiae has been a useful model organism for the study of cell wall synthesis, and over the past few decades, many aspects of the composition, structure, and enzymology of the cell wall have been elucidated. The cell wall of budding yeasts is a complex and dynamic structure; its arrangement alters as the cell grows, and its composition changes in response to different environmental conditions and at different times during the yeast life cycle. In the past few years, we have witnessed a profilic genetic and molecular characterization of some key aspects of cell wall polymer synthesis and hydrolysis in the budding yeast. Furthermore, this organism has been the target of numerous recent studies on the topic of morphogenesis, which have had an enormous impact on our understanding of the intracellular events that participate in directed cell wall synthesis. A number of components that direct polarized secretion, including those involved in assembly and organization of the actin cytoskeleton, secretory pathways, and a series of novel signal transduction systems and regulatory components have been identified. Analysis of these different components has suggested pathways by which polarized secretion is directed and controlled. Our aim is to offer an overall view of the current understanding of cell wall dynamics and of the complex network that controls polarized growth at particular stages of the budding yeast cell cycle and life cycle. PMID:7565410

  3. Coliphage P1 morphogenesis: analysis of mutants by electron microscopy.

    PubMed Central

    Walker, J T; Walker, D H

    1983-01-01

    We used electron microscopy and serum blocking power tests to determine the phenotypes of 47 phage P1 amber mutants that have defects in particle morphogenesis. Eleven mutants showed head defects, 30 showed tail defects, and 6 had a defect in particle maturation (which could be either in the head or in the tail). Consideration of previous complementation test results, genetic and physical positions of the mutations, and phenotypes of the mutants allowed assignment of most of the 47 mutations to genes. Thus, a minimum of 12 tail genes, 4 head genes, and 1 particle maturation gene are now known for P1. Of the 12 tail genes, 1 (gene 19, located within the invertible C loop) codes for tail fibers, 6 (genes 3, 5, 16, 20, 21, and 26) code for baseplate components (although one of these genes could code for the tail tube), 1 (gene 22) codes for the sheath, 1 (gene 6) affects tail length, 2 (genes 7 and 25) are involved in tail stability, and 1 (gene 24) either codes for a baseplate component or is involved in tail stability. Of the four head genes, gene 9 codes for a protein required for DNA packaging. The function of head gene 4 is unclear. Head gene 8 probably codes for a minor head protein, whereas head gene 23 could code for either a minor head protein or the major head protein. Excluding the particle maturation gene (gene 1), the 12 tail genes are clustered in three regions of the P1 physical genome. The four head genes are at four separate locations. However, some P1 head genes have not yet been detected and could be located in two regions (for which there are no known genes) adjacent to genes 4 and 8. The P1 morphogenetic gene clusters are interrupted by many genes that are expressed in the prophage. Images PMID:6834479

  4. Coordinating cardiomyocyte interactions to direct ventricular chamber morphogenesis.

    PubMed

    Han, Peidong; Bloomekatz, Joshua; Ren, Jie; Zhang, Ruilin; Grinstein, Jonathan D; Zhao, Long; Burns, C Geoffrey; Burns, Caroline E; Anderson, Ryan M; Chi, Neil C

    2016-06-29

    Many organs are composed of complex tissue walls that are structurally organized to optimize organ function. In particular, the ventricular myocardial wall of the heart comprises an outer compact layer that concentrically encircles the ridge-like inner trabecular layer. Although disruption in the morphogenesis of this myocardial wall can lead to various forms of congenital heart disease and non-compaction cardiomyopathies, it remains unclear how embryonic cardiomyocytes assemble to form ventricular wall layers of appropriate spatial dimensions and myocardial mass. Here we use advanced genetic and imaging tools in zebrafish to reveal an interplay between myocardial Notch and Erbb2 signalling that directs the spatial allocation of myocardial cells to their proper morphological positions in the ventricular wall. Although previous studies have shown that endocardial Notch signalling non-cell-autonomously promotes myocardial trabeculation through Erbb2 and bone morphogenetic protein (BMP) signalling, we discover that distinct ventricular cardiomyocyte clusters exhibit myocardial Notch activity that cell-autonomously inhibits Erbb2 signalling and prevents cardiomyocyte sprouting and trabeculation. Myocardial-specific Notch inactivation leads to ventricles of reduced size and increased wall thickness because of excessive trabeculae, whereas widespread myocardial Notch activity results in ventricles of increased size with a single-cell-thick wall but no trabeculae. Notably, this myocardial Notch signalling is activated non-cell-autonomously by neighbouring Erbb2-activated cardiomyocytes that sprout and form nascent trabeculae. Thus, these findings support an interactive cellular feedback process that guides the assembly of cardiomyocytes to morphologically create the ventricular myocardial wall and more broadly provide insight into the cellular dynamics of how diverse cell lineages organize to create form.

  5. Morphogenesis of the C. elegans Intestine Involves Axon Guidance Genes

    PubMed Central

    Asan, Alparsan; Raiders, Stephan A.; Priess, James R.

    2016-01-01

    Genetic and molecular studies have provided considerable insight into how various tissue progenitors are specified in early embryogenesis, but much less is known about how those progenitors create three-dimensional tissues and organs. The C. elegans intestine provides a simple system for studying how a single progenitor, the E blastomere, builds an epithelial tube of 20 cells. As the E descendants divide, they form a primordium that transitions between different shapes over time. We used cell contours, traced from confocal optical z-stacks, to build a 3D graphic reconstruction of intestine development. The reconstruction revealed several new aspects of morphogenesis that extend and clarify previous observations. The first 8 E descendants form a plane of four right cells and four left cells; the plane arises through oriented cell divisions and VANG-1/Van Gogh-dependent repositioning of any non-planar cells. LIN-12/Notch signaling affects the left cells in the E8 primordium, and initiates later asymmetry in cell packing. The next few stages involve cell repositioning and intercalation events that shuttle cells to their final positions, like shifting blocks in a Rubik’s cube. Repositioning involves breaking and replacing specific adhesive contacts, and some of these events involve EFN-4/Ephrin, MAB-20/semaphorin-2a, and SAX-3/Robo. Once cells in the primordium align along a common axis and in the correct order, cells at the anterior end rotate clockwise around the axis of the intestine. The anterior rotation appears to align segments of the developing lumen into a continuous structure, and requires the secreted ligand UNC-6/netrin, the receptor UNC-40/DCC, and an interacting protein called MADD-2. Previous studies showed that rotation requires a second round of LIN-12/Notch signaling in cells on the right side of the primordium, and we show that MADD-2-GFP appears to be downregulated in those cells. PMID:27035721

  6. Morphogenesis of the C. elegans Intestine Involves Axon Guidance Genes.

    PubMed

    Asan, Alparsan; Raiders, Stephan A; Priess, James R

    2016-04-01

    Genetic and molecular studies have provided considerable insight into how various tissue progenitors are specified in early embryogenesis, but much less is known about how those progenitors create three-dimensional tissues and organs. The C. elegans intestine provides a simple system for studying how a single progenitor, the E blastomere, builds an epithelial tube of 20 cells. As the E descendants divide, they form a primordium that transitions between different shapes over time. We used cell contours, traced from confocal optical z-stacks, to build a 3D graphic reconstruction of intestine development. The reconstruction revealed several new aspects of morphogenesis that extend and clarify previous observations. The first 8 E descendants form a plane of four right cells and four left cells; the plane arises through oriented cell divisions and VANG-1/Van Gogh-dependent repositioning of any non-planar cells. LIN-12/Notch signaling affects the left cells in the E8 primordium, and initiates later asymmetry in cell packing. The next few stages involve cell repositioning and intercalation events that shuttle cells to their final positions, like shifting blocks in a Rubik's cube. Repositioning involves breaking and replacing specific adhesive contacts, and some of these events involve EFN-4/Ephrin, MAB-20/semaphorin-2a, and SAX-3/Robo. Once cells in the primordium align along a common axis and in the correct order, cells at the anterior end rotate clockwise around the axis of the intestine. The anterior rotation appears to align segments of the developing lumen into a continuous structure, and requires the secreted ligand UNC-6/netrin, the receptor UNC-40/DCC, and an interacting protein called MADD-2. Previous studies showed that rotation requires a second round of LIN-12/Notch signaling in cells on the right side of the primordium, and we show that MADD-2-GFP appears to be downregulated in those cells.

  7. Biocompatible tissue scaffold compliance promotes salivary gland morphogenesis and differentiation.

    PubMed

    Peters, Sarah B; Naim, Nyla; Nelson, Deirdre A; Mosier, Aaron P; Cady, Nathaniel C; Larsen, Melinda

    2014-06-01

    Substrate compliance is reported to alter cell phenotype, but little is known about the effects of compliance on cell development within the context of a complex tissue. In this study, we used 0.48 and 19.66 kPa polyacrylamide gels to test the effects of the substrate modulus on submandibular salivary gland development in culture and found a significant decrease in branching morphogenesis in explants grown on the stiff 19.66 kPa gels relative to those grown on the more physiologically compliant 0.48 kPa gels. While proliferation and apoptosis were not affected by the substrate modulus, tissue architecture and epithelial acinar cell differentiation were profoundly perturbed by aberrant, high stiffness. The glands cultured on 0.48 kPa gels were similar to developing glands in morphology and expression of the differentiation markers smooth muscle alpha-actin (SM α-actin) in developing myoepithelial cells and aquaporin 5 (AQP5) in proacinar cells. At 19.66 kPa, however, tissue morphology and the expression and distribution of SM α-actin and AQP5 were disrupted. Significantly, aberrant gland development at 19.66 kPa could be rescued by both mechanical and chemical stimuli. Transfer of glands from 19.66 to 0.48 kPa gels resulted in substantial recovery of acinar structure and differentiation, and addition of exogenous transforming growth factor beta 1 at 19.66 kPa resulted in a partial rescue of morphology and differentiation within the proacinar buds. These results indicate that environmental compliance is critical for organogenesis, and suggest that both mechanical and chemical stimuli can be exploited to promote organ development in the contexts of tissue engineering and organ regeneration.

  8. Coordinating cardiomyocyte interactions to direct ventricular chamber morphogenesis.

    PubMed

    Han, Peidong; Bloomekatz, Joshua; Ren, Jie; Zhang, Ruilin; Grinstein, Jonathan D; Zhao, Long; Burns, C Geoffrey; Burns, Caroline E; Anderson, Ryan M; Chi, Neil C

    2016-06-30

    Many organs are composed of complex tissue walls that are structurally organized to optimize organ function. In particular, the ventricular myocardial wall of the heart comprises an outer compact layer that concentrically encircles the ridge-like inner trabecular layer. Although disruption in the morphogenesis of this myocardial wall can lead to various forms of congenital heart disease and non-compaction cardiomyopathies, it remains unclear how embryonic cardiomyocytes assemble to form ventricular wall layers of appropriate spatial dimensions and myocardial mass. Here we use advanced genetic and imaging tools in zebrafish to reveal an interplay between myocardial Notch and Erbb2 signalling that directs the spatial allocation of myocardial cells to their proper morphological positions in the ventricular wall. Although previous studies have shown that endocardial Notch signalling non-cell-autonomously promotes myocardial trabeculation through Erbb2 and bone morphogenetic protein (BMP) signalling, we discover that distinct ventricular cardiomyocyte clusters exhibit myocardial Notch activity that cell-autonomously inhibits Erbb2 signalling and prevents cardiomyocyte sprouting and trabeculation. Myocardial-specific Notch inactivation leads to ventricles of reduced size and increased wall thickness because of excessive trabeculae, whereas widespread myocardial Notch activity results in ventricles of increased size with a single-cell-thick wall but no trabeculae. Notably, this myocardial Notch signalling is activated non-cell-autonomously by neighbouring Erbb2-activated cardiomyocytes that sprout and form nascent trabeculae. Thus, these findings support an interactive cellular feedback process that guides the assembly of cardiomyocytes to morphologically create the ventricular myocardial wall and more broadly provide insight into the cellular dynamics of how diverse cell lineages organize to create form. PMID:27357797

  9. Mathematical Modeling of Branching Morphogenesis and Vascular Tumor Growth

    NASA Astrophysics Data System (ADS)

    Yan, Huaming

    Feedback regulation of cell lineages is known to play an important role in tissue size control, but the effect in tissue morphogenesis has yet to be explored. We first use a non-spatial model to show that a combination of positive and negative feedback on stem and/or progenitor cell self-renewal leads to bistable or bi-modal growth behaviors and ultrasensitivity to external growth cues. Next, a spatiotemporal model is used to demonstrate spatial patterns such as local budding and branching arise in this setting, and are not consequences of Turing-type instabilities. We next extend the model to a three-dimensional hybrid discrete-continuum model of tumor growth to study the effects of angiogenesis, tumor progression and cancer therapies. We account for the crosstalk between the vasculature and cancer stem cells (CSCs), and CSC transdifferentiation into vascular endothelial cells (gECs), as observed experimentally. The vasculature stabilizes tumor invasiveness but considerably enhances growth. A gEC network structure forms spontaneously within the hypoxic core, consistent with experimental findings. The model is then used to study cancer therapeutics. We demonstrate that traditional anti-angiogenic therapies decelerate tumor growth, but make the tumor highly invasive. Chemotherapies help to reduce tumor sizes, but cannot control the invasion. Anti-CSC therapies that promote differentiation or disturb the stem cell niche effectively reduce tumor invasiveness. However, gECs inherit mutations present in CSCs and are resistant to traditional therapies. We show that anti-gEC treatments block the support on CSCs by gECs, and reduce both tumor size and invasiveness. Our study suggests that therapies targeting the vasculature, CSCs and gECs, when combined, are highly synergistic and are capable of controlling both tumor size and shape.

  10. Pneumococcal Vertebral Osteomyelitis after Epidural Injection: A Rare Event

    PubMed Central

    Johnson, Tamara M; Chitturi, Chandrika; Lange, Michael; Suh, Jin S; Slim, Jihad

    2016-01-01

    Streptococcus pneumoniae vertebral infections have rarely been reported. Herein, we report a case of pneumococcal vertebral osteomyelitis with paraspinal and epidural abscesses as well as concomitant bacteremia following epidural injection. This will be the second case in the literature reporting pneumococcal vertebral osteomyelitis related to epidural manipulation. PMID:27621563

  11. Pneumococcal Vertebral Osteomyelitis after Epidural Injection: A Rare Event.

    PubMed

    Johnson, Tamara M; Chitturi, Chandrika; Lange, Michael; Suh, Jin S; Slim, Jihad

    2016-01-01

    Streptococcus pneumoniae vertebral infections have rarely been reported. Herein, we report a case of pneumococcal vertebral osteomyelitis with paraspinal and epidural abscesses as well as concomitant bacteremia following epidural injection. This will be the second case in the literature reporting pneumococcal vertebral osteomyelitis related to epidural manipulation. PMID:27621563

  12. The variety of vertebrate mechanisms of sex determination.

    PubMed

    Trukhina, Antonina V; Lukina, Natalia A; Wackerow-Kouzova, Natalia D; Smirnov, Alexander F

    2013-01-01

    The review deals with features of sex determination in vertebrates. The mechanisms of sex determination are compared between fishes, amphibians, reptilians, birds, and mammals. We focus on structural and functional differences in the role of sex-determining genes in different vertebrates. Special attention is paid to the role of estrogens in sex determination in nonmammalian vertebrates. PMID:24369014

  13. Vertebral Augmentation Involving Vertebroplasty or Kyphoplasty for Cancer-Related Vertebral Compression Fractures: An Economic Analysis

    PubMed Central

    2016-01-01

    Background Untreated vertebral compression fractures can have serious clinical consequences and impose a considerable impact on patients' quality of life and on caregivers. Since non-surgical management of these fractures has limited effectiveness, vertebral augmentation procedures are gaining acceptance in clinical practice for pain control and fracture stabilization. The objective of this analysis was to determine the cost-effectiveness and budgetary impact of kyphoplasty or vertebroplasty compared with non-surgical management for the treatment of vertebral compression fractures in patients with cancer. Methods We performed a systematic review of health economic studies to identify relevant studies that compare the cost-effectiveness of kyphoplasty or vertebroplasty with non-surgical management for the treatment of vertebral compression fractures in adults with cancer. We also performed a primary cost-effectiveness analysis to assess the clinical benefits and costs of kyphoplasty or vertebroplasty compared with non-surgical management in the same population. We developed a Markov model to forecast benefits and harms of treatments, and corresponding quality-adjusted life years and costs. Clinical data and utility data were derived from published sources, while costing data were derived using Ontario administrative sources. We performed sensitivity analyses to examine the robustness of the results. In addition, a 1-year budget impact analysis was performed using data from Ontario administrative sources. Two scenarios were explored: (a) an increase in the total number of vertebral augmentation procedures performed among patients with cancer in Ontario, maintaining the current proportion of kyphoplasty versus vertebroplasty; and (b) no increase in the total number of vertebral augmentation procedures performed among patients with cancer in Ontario but an increase in the proportion of kyphoplasties versus vertebroplasties. Results The base case considered each of

  14. Vertebral Augmentation Involving Vertebroplasty or Kyphoplasty for Cancer-Related Vertebral Compression Fractures: A Systematic Review

    PubMed Central

    2016-01-01

    Background Cancers that metastasize to the spine and primary cancers such as multiple myeloma can result in vertebral compression fractures or instability. Conservative strategies, including bed rest, bracing, and analgesic use, can be ineffective, resulting in continued pain and progressive functional disability limiting mobility and self-care. Surgery is not usually an option for cancer patients in advanced disease states because of their poor medical health or functional status and limited life expectancy. The objectives of this review were to evaluate the effectiveness and safety of percutaneous image-guided vertebral augmentation techniques, vertebroplasty and kyphoplasty, for palliation of cancer-related vertebral compression fractures. Methods We performed a systematic literature search for studies on vertebral augmentation of cancer-related vertebral compression fractures published from January 1, 2000, to October 2014; abstracts were screened by a single reviewer. For those studies meeting the eligibility criteria, full-text articles were obtained. Owing to the heterogeneity of the clinical reports, we performed a narrative synthesis based on an analytical framework constructed for the type of cancer-related vertebral fractures and the diversity of the vertebral augmentation interventions. Results The evidence review identified 3,391 citations, of which 111 clinical reports (4,235 patients) evaluated the effectiveness of vertebroplasty (78 reports, 2,545 patients) or kyphoplasty (33 reports, 1,690 patients) for patients with mixed primary spinal metastatic cancers, multiple myeloma, or hemangiomas. Overall the mean pain intensity scores often reported within 48 hours of vertebral augmentation (kyphoplasty or vertebroplasty), were significantly reduced. Analgesic use, although variably reported, usually involved parallel decreases, particularly in opioids, and mean pain-related disability scores were also significantly improved. In a randomized controlled

  15. YAP is essential for tissue tension to ensure vertebrate 3D body shape.

    PubMed

    Porazinski, Sean; Wang, Huijia; Asaoka, Yoichi; Behrndt, Martin; Miyamoto, Tatsuo; Morita, Hitoshi; Hata, Shoji; Sasaki, Takashi; Krens, S F Gabriel; Osada, Yumi; Asaka, Satoshi; Momoi, Akihiro; Linton, Sarah; Miesfeld, Joel B; Link, Brian A; Senga, Takeshi; Castillo-Morales, Atahualpa; Urrutia, Araxi O; Shimizu, Nobuyoshi; Nagase, Hideaki; Matsuura, Shinya; Bagby, Stefan; Kondoh, Hisato; Nishina, Hiroshi; Heisenberg, Carl-Philipp; Furutani-Seiki, Makoto

    2015-05-14

    Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape. Understanding this morphogenetic function of YAP could facilitate the use of embryonic stem cells to generate complex organs requiring correct alignment of multiple tissues.

  16. Early Divergence of Central and Peripheral Neural Retina Precursors During Vertebrate Eye Development

    PubMed Central

    Venters, Sara J.; Mikawa, Takashi; Hyer, Jeanette

    2015-01-01

    During development of the vertebrate eye, optic tissue is progressively compartmentalized into functionally distinct tissues. From the central to the peripheral optic cup, the original optic neuroepithelial tissue compartmentalizes, forming retina, ciliary body and iris. The retina can be further sub-divided into peripheral and central compartments, where the central domain is specialized for higher visual acuity, having a higher ratio and density of cone photoreceptors in most species. Classically, models depict a segregation of the early optic cup into only two domains, neural and non-neural. Recent studies, however, uncovered discrete precursors for central and peripheral retina in the optic vesicle, indicating that the neural retina cannot be considered as a single unit with homogeneous specification and development. Instead, central and peripheral retina may be subject to distinct developmental pathways that underlie their specialization. This review focuses on lineage relationships in the retina and revisits the historical context for segregation of central and peripheral retina precursors before overt eye morphogenesis. PMID:25329498

  17. Species sensitivity distribution approach to primary risk analysis of the metal pyrithione photodegradation product, 2,2'-dipyridyldisulfide in the Inland Sea and induction of notochord undulation in fish embryos.

    PubMed

    Mochida, Kazuhiko; Amano, Haruna; Ito, Katsutoshi; Ito, Mana; Onduka, Toshimitsu; Ichihashi, Hideki; Kakuno, Akira; Harino, Hiroya; Fujii, Kazunori

    2012-08-15

    To carry out a primary risk assessment in the Inland Sea of Japan for 2,2'-dipyridyldisulfide [(PS)(2)], a metal pyrithione photodegradation product, we used a methodology based on the species sensitivity distribution (SSD) estimated with a Bayesian statistical model. We first conducted growth inhibition tests with three marine phytoplankton species, Tetraselmis tetrathele, Chaetoceros calcitrans, and Dunaliella tertiolecta. We also performed acute and early life stage toxicity (ELS) tests with a teleost fish, the mummichog (Fundulus heteroclitus). The algal growth inhibition tests revealed that the 72-h EC(50) ranged from 62 to 1100 μg/L. Acute toxicity tests with larval mummichogs revealed that the 96-h LC(50) was approximately 500 μg/L based on the actual toxicant concentrations. ELS testing of (PS)(2) under continuous flow-through conditions for 50 days revealed that growth was the most sensitive endpoint, and both total length and body weight were significantly lower in the groups exposed to 27 μg/L (PS)(2) compared to the solvent control group. We determined a lowest observed effect concentration of 17 μg/L and a NOEC of 5.9 μg/L based on the actual toxicant concentrations. By using the ecotoxicity data (LC(50) and EC(50)) from this study and previous work, we calculated a hazardous concentration that should protect 95% and 99% of species (HC(5) and HC(1)) based on the SSD derived with a Bayesian statistical model. The medians with 90% confidence intervals (parentheses) of the HC(5) and HC(1) were 31.0 (3.2, 101.8) μg/L and 10.1 (0.5, 44.2) μg/L, respectively. In the ELS test, about 80% of hatched larvae exposed to 243-μg/L (PS)(2) displayed a notochord undulation. To elucidate the cause of the notochord undulation, we carried out embryo toxicity tests by exposing embryos at various developmental stages to (PS)(2). Exposure to (PS)(2) through the entire gastrulae stage was important to induction of the morphological abnormality. Lysyl oxidase activity

  18. Vertebral destruction due to abdominal aortic aneurysm

    PubMed Central

    Jiménez Viseu Pinheiro, J.F.; Blanco Blanco, J.F.; Pescador Hernández, D.; García García, F.J.

    2014-01-01

    Introduction Low back pain is a common cause of medical consultation, and usually supposes a non-malignant prognostic. Presentation of case We report an atypical appearance of low back pain associated to shock and pulsatile abdominal mass that made us diagnose an abdominal aortic aneurysm as reason of vertebral lysis and pain. Discusion Surgical repair of contained AAA should be directed to secondary re-rupture prevention, with an approximate survival near to 100% at selected patients for elective surgery. Consequently, orthopedic surgery for back spine stabilization has to be elective in those cases when vertebral destruction is above 30% and clinic is directly related to spine instability. Conclusion We should consider AAA as other cause of low back pain and routinely examine the abdomen and seek complementary imaging proves when risk factors for AAA are present. PMID:25569196

  19. Patterns and Processes of Vertebrate Evolution

    NASA Astrophysics Data System (ADS)

    Carroll, Robert Lynn

    1997-04-01

    This new text provides an integrated view of the forces that influence the patterns and rates of vertebrate evolution from the level of living populations and species to those that resulted in the origin of the major vertebrate groups. The evolutionary roles of behavior, development, continental drift, and mass extinctions are compared with the importance of variation and natural selection that were emphasized by Darwin. It is extensively illustrated, showing major transitions between fish and amphibians, dinosaurs and birds, and land mammals to whales. No book since Simpson's Major Features of Evolution has attempted such a broad study of the patterns and forces of evolutionary change. Undergraduate students taking a general or advanced course on evolution, and graduate students and professionals in evolutionary biology and paleontology will find the book of great interest.

  20. Acute compressive myelopathy due to vertebral haemangioma.

    PubMed

    Macki, Mohamed; Bydon, Mohamad; Kaloostian, Paul; Bydon, Ali

    2014-04-28

    A 47-year-old woman with a history of anaemia presented to the emergency room with an acute onset of leg weakness. Physical examination of the bilateral lower extremities was significant for 0/5 muscle strength in all muscle groups with decreased pinprick and temperature sensation. A sensory level at the umbilicus was appreciated. Fine touch and proprioception were preserved. Bowel and bladder function were intact. CT revealed several thoracic, vertebral haemangiomatas. An MRI was suggestive of an epidural clot at the T8-T10-weighted posterior epidural space. At the level of the lesion, the cerebrospinal fluid space was completely effaced, and the flattened spinal cord exhibited signs of oedema and compressive myelopathy. The patient immediately underwent surgical decompression of the spinal cord. An epidural clot and vessel conglomeration were identified. A postoperative spinal angiogram confirmed the diagnosis of vertebral haemangioma. At 1-month follow-up, the patient regained strength and sensation.

  1. Brain size varies with temperature in vertebrates.

    PubMed

    Gillooly, James F; McCoy, Michael W

    2014-01-01

    The tremendous variation in brain size among vertebrates has long been thought to be related to differences in species' metabolic rates. It is thought that species with higher metabolic rates can supply more energy to support the relatively high cost of brain tissue. And yet, while body temperature is known to be a major determinant of metabolic rate, the possible effects of temperature on brain size have scarcely been explored. Thus, here we explore the effects of temperature on brain size among diverse vertebrates (fishes, amphibians, reptiles, birds and mammals). We find that, after controlling for body size, brain size increases exponentially with temperature in much the same way as metabolic rate. These results suggest that temperature-dependent changes in aerobic capacity, which have long been known to affect physical performance, similarly affect brain size. The observed temperature-dependence of brain size may explain observed gradients in brain size among both ectotherms and endotherms across broad spatial and temporal scales.

  2. Miocene vertebrates and North Florida shorelines

    USGS Publications Warehouse

    Olsen, S.J.

    1968-01-01

    Vertebrate fossils from ten localities, spread across northern Florida, give evidence of shorelines and deltas that have previously been established on geologic evidence or invertebrates alone. Terrestrial mammal remains, in association with shallow-water forms, indicate a deltaic assemblage and in several instances specific animals suggest restricted water depths at the time of sediment deposition. Fortunately diagnostic fragments of Miocene horses, Merychippus and Parahippus, are present in these beds, allowing for a rather close age evaluation of these sediments. Adequate fossil material has been collected from these localities to suggest the past environment and ecological conditions for the forms represented. By utilizing a suggested course of experiments with stream table apparatus it is possible to use the orientation of the fossil vertebrate remains as aids in determining past conditions of sediment accumulation. ?? 1968.

  3. Population momentum across vertebrate life histories

    USGS Publications Warehouse

    Koons, D.N.; Grand, J.B.; Arnold, J.M.

    2006-01-01

    Population abundance is critically important in conservation, management, and demographic theory. Thus, to better understand how perturbations to the life history affect long-term population size, we examined population momentum for four vertebrate classes with different life history strategies. In a series of demographic experiments we show that population momentum generally has a larger effect on long-term population size for organisms with long generation times than for organisms with short generation times. However, patterns between population momentum and generation time varied across taxonomic groups and according to the life history parameter that was changed. Our findings indicate that momentum may be an especially important aspect of population dynamics for long-lived vertebrates, and deserves greater attention in life history studies. Further, we discuss the importance of population momentum in natural resource management, pest control, and conservation arenas. ?? 2006 Elsevier B.V. All rights reserved.

  4. Turning Heads: Development of Vertebrate Branchiomotor Neurons

    PubMed Central

    Chandrasekhar, Anand

    2007-01-01

    The cranial motor neurons innervate muscles that control eye, jaw, and facial movements of the vertebrate head and parasympathetic neurons that innervate certain glands and organs. These efferent neurons develop at characteristic locations in the brainstem, and their axons exit the neural tube in well-defined trajectories to innervate target tissues. This review is focused on a subset of cranial motor neurons called the branchiomotor neurons, which innervate muscles derived from the branchial (pharyngeal) arches. First, the organization of the branchiomotor pathways in zebrafish, chick, and mouse embryos will be compared, and the underlying axon guidance mechanisms will be addressed. Next, the molecular mechanisms that generate branchiomotor neurons and specify their identities will be discussed. Finally, the caudally directed or tangential migration of facial branchiomotor neurons will be examined. Given the advances in the characterization and analysis of vertebrate genomes, we can expect rapid progress in elucidating the cellular and molecular mechanisms underlying the development of these vital neuronal networks. PMID:14699587

  5. Photoreceptor cell fate specification in vertebrates

    PubMed Central

    Brzezinski, Joseph A.; Reh, Thomas A.

    2015-01-01

    Photoreceptors – the light-sensitive cells in the vertebrate retina – have been extremely well-characterized with regards to their biochemistry, cell biology and physiology. They therefore provide an excellent model for exploring the factors and mechanisms that drive neural progenitors into a differentiated cell fate in the nervous system. As a result, great progress in understanding the transcriptional network that controls photoreceptor specification and differentiation has been made over the last 20 years. This progress has also enabled the production of photoreceptors from pluripotent stem cells, thereby aiding the development of regenerative medical approaches to eye disease. In this Review, we outline the signaling and transcription factors that drive vertebrate photoreceptor development and discuss how these function together in gene regulatory networks to control photoreceptor cell fate specification. PMID:26443631

  6. An aboral-dorsalization hypothesis for chordate origin.

    PubMed

    Satoh, Nori

    2008-11-01

    Chordates originated from a common ancestor(s) shared with two other deuterostome groups, echinoderms and hemichordates, by creating a novel type of tadpole-like larva, which was characterized by a dorsal hollow neural tube and notochord. Recent molecular phylogeny supports the notion that echinoderms and hemichordates form a clade named the Ambulacraria and that, among the chordates, cephalochordates are more basal than urochordates and vertebrates. An aboral-dorsalization hypothesis is proposed to explain how the tadpole-type larva evolved. Embryological comparison of cephalochordates with nonchordate deuterostomes suggests that, because of limited space on the oral side of the ancestral embryo, morphogenesis to form the neural tube and notochord occurred on the aboral side of the embryo. Namely, the dorsalization of the aboral side of the ancestral embryo may have been a key developmental event that led to the formation of the basic chordate body plan.

  7. A critical role for sonic hedgehog signaling in the early expansion of the developing brain.

    PubMed

    Britto, Joanne; Tannahill, David; Keynes, Roger

    2002-02-01

    The mechanisms that coordinate the three-dimensional shape of the vertebrate brain during development are largely unknown. We have found that sonic hedgehog (Shh) is crucial in driving the rapid, extensive expansion of the early vesicles of the developing midbrain and forebrain. Transient displacement of the notochord from the midbrain floor plate resulted in abnormal folding and overall collapse of the vesicles, accompanied by reduced cell proliferation and increased cell death in the midbrain. Simultaneously, expression of Shh decreased locally in the notochord and floor plate, whereas overt patterning and differentiation proceeded normally. Normal midbrain expansion was restored by implantation of Shh-secreting cells in a dose-dependent manner; conversely, expansion was retarded following antagonism of the Shh signaling pathway by cyclopamine. Our results indicate that Shh signaling from the ventral midline is essential for regulating brain morphogenesis during early development.

  8. On multiscale approaches to three-dimensional modelling of morphogenesis

    PubMed Central

    Chaturvedi, R; Huang, C; Kazmierczak, B; Schneider, T; Izaguirre, J.A; Glimm, T; Hentschel, H.G.E; Glazier, J.A; Newman, S.A; Alber, M.S

    2005-01-01

    In this paper we present the foundation of a unified, object-oriented, three-dimensional biomodelling environment, which allows us to integrate multiple submodels at scales from subcellular to those of tissues and organs. Our current implementation combines a modified discrete model from statistical mechanics, the Cellular Potts Model, with a continuum reaction–diffusion model and a state automaton with well-defined conditions for cell differentiation transitions to model genetic regulation. This environment allows us to rapidly and compactly create computational models of a class of complex-developmental phenomena. To illustrate model development, we simulate a simplified version of the formation of the skeletal pattern in a growing embryonic vertebrate limb. PMID:16849182

  9. klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis

    PubMed Central

    Steed, Emily; Faggianelli, Nathalie; Roth, Stéphane; Ramspacher, Caroline; Concordet, Jean-Paul; Vermot, Julien

    2016-01-01

    The heartbeat and blood flow signal to endocardial cell progenitors through mechanosensitive proteins that modulate the genetic program controlling heart valve morphogenesis. To date, the mechanism by which mechanical forces coordinate tissue morphogenesis is poorly understood. Here we use high-resolution imaging to uncover the coordinated cell behaviours leading to heart valve formation. We find that heart valves originate from progenitors located in the ventricle and atrium that generate the valve leaflets through a coordinated set of endocardial tissue movements. Gene profiling analyses and live imaging reveal that this reorganization is dependent on extracellular matrix proteins, in particular on the expression of fibronectin1b. We show that blood flow and klf2a, a major endocardial flow-responsive gene, control these cell behaviours and fibronectin1b synthesis. Our results uncover a unique multicellular layering process leading to leaflet formation and demonstrate that endocardial mechanotransduction and valve morphogenesis are coupled via cellular rearrangements mediated by fibronectin synthesis. PMID:27221222

  10. The kinase regulator mob1 acts as a patterning protein for stentor morphogenesis.

    PubMed

    Slabodnick, Mark M; Ruby, J Graham; Dunn, Joshua G; Feldman, Jessica L; DeRisi, Joseph L; Marshall, Wallace F

    2014-05-01

    Morphogenesis and pattern formation are vital processes in any organism, whether unicellular or multicellular. But in contrast to the developmental biology of plants and animals, the principles of morphogenesis and pattern formation in single cells remain largely unknown. Although all cells develop patterns, they are most obvious in ciliates; hence, we have turned to a classical unicellular model system, the giant ciliate Stentor coeruleus. Here we show that the RNA interference (RNAi) machinery is conserved in Stentor. Using RNAi, we identify the kinase coactivator Mob1--with conserved functions in cell division and morphogenesis from plants to humans-as an asymmetrically localized patterning protein required for global patterning during development and regeneration in Stentor. Our studies reopen the door for Stentor as a model regeneration system. PMID:24823688

  11. The ureteric bud epithelium: Morphogenesis and roles in metanephric kidney patterning

    PubMed Central

    Nagalakshmi, Vidya K.; Yu, Jing

    2015-01-01

    The mammalian metanephric kidney is composed of two epithelial components –the collecting duct system and the nephron epithelium– that differentiate from two different tissues –the ureteric bud epithelium and the nephron progenitors, respectively– of intermediate mesoderm origin. The collecting duct system is generated through reiterative ureteric bud branching morphogenesis whereas the nephron epithelium is formed in a process termed nephrogenesis, which is initiated with the mesenchymal-epithelial transition of the nephron progenitors. Ureteric bud branching morphogenesis is regulated by nephron progenitors, and in return the ureteric bud epithelium regulates nephrogenesis. The metanephric kidney is also physiologically divided along the cortico-medullary axis into subcompartments that are enriched with specific segments of these two epithelial structures. Here we provide an overview of the major molecular and cellular processes underlying the morphogenesis and patterning of the ureteric bud epithelium and its roles in the cortical-medullary patterning of the metanephric kidney. PMID:25783232

  12. A STRIPAK component Strip regulates neuronal morphogenesis by affecting microtubule stability

    PubMed Central

    Sakuma, Chisako; Okumura, Misako; Umehara, Tomoki; Miura, Masayuki; Chihara, Takahiro

    2015-01-01

    During neural development, regulation of microtubule stability is essential for proper morphogenesis of neurons. Recently, the striatin-interacting phosphatase and kinase (STRIPAK) complex was revealed to be involved in diverse cellular processes. However, there is little evidence that STRIPAK components regulate microtubule dynamics, especially in vivo. Here, we show that one of the core STRIPAK components, Strip, is required for microtubule organization during neuronal morphogenesis. Knockdown of Strip causes a decrease in the level of acetylated α-tubulin in Drosophila S2 cells, suggesting that Strip influences the stability of microtubules. We also found that Strip physically and genetically interacts with tubulin folding cofactor D (TBCD), an essential regulator of α- and β-tubulin heterodimers. Furthermore, we demonstrate the genetic interaction between strip and Down syndrome cell adhesion molecule (Dscam), a cell surface molecule that is known to work with TBCD. Thus, we propose that Strip regulates neuronal morphogenesis by affecting microtubule stability. PMID:26644129

  13. Capillary morphogenesis during human endothelial cell invasion of three-dimensional collagen matrices.

    PubMed

    Davis, G E; Black, S M; Bayless, K J

    2000-09-01

    Here, we describe assay systems that utilize serum-free defined media to evaluate capillary morphogenesis during human endothelial cell (EC) invasion of three-dimensional collagen matrices. ECs invade these matrices over a 1-3-d period to form capillary tubes. Blocking antibodies to the alpha2beta1 integrin interfere with invasion and morphogenesis while other integrin blocking antibodies do not. Interestingly, we observed increased invasion of ECs toward a population of underlying ECs undergoing morphogenesis. In addition, we have developed assays on microscope slides that display the invasion process horizontally, thereby enhancing our ability to image these events. Thus far, we have observed intracellular vacuoles that appear to regulate the formation of capillary lumens, and extensive cell processes that facilitate the interconnection of ECs during morphogenic events. These assays should enable further investigation of the morphologic steps and molecular events controlling human capillary tube formation in three-dimensional extracellular matrices.

  14. The Kinase Regulator Mob1 Acts as a Patterning Protein for Stentor Morphogenesis

    PubMed Central

    Slabodnick, Mark M.; Ruby, J. Graham; Dunn, Joshua G.; Feldman, Jessica L.; DeRisi, Joseph L.; Marshall, Wallace F.

    2014-01-01

    Morphogenesis and pattern formation are vital processes in any organism, whether unicellular or multicellular. But in contrast to the developmental biology of plants and animals, the principles of morphogenesis and pattern formation in single cells remain largely unknown. Although all cells develop patterns, they are most obvious in ciliates; hence, we have turned to a classical unicellular model system, the giant ciliate Stentor coeruleus. Here we show that the RNA interference (RNAi) machinery is conserved in Stentor. Using RNAi, we identify the kinase coactivator Mob1—with conserved functions in cell division and morphogenesis from plants to humans—as an asymmetrically localized patterning protein required for global patterning during development and regeneration in Stentor. Our studies reopen the door for Stentor as a model regeneration system. PMID:24823688

  15. Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium

    PubMed Central

    Magenheim, Judith; Klein, Allon M.; Stanger, Ben Z.; Ashery-Padan, Ruth; Sosa-Pineda, Beatriz; Gu, Guoqiang; Dor, Yuval

    2013-01-01

    Summary During pancreas development, endocrine and exocrine cells arise from a common multipotent progenitor pool. How these cell fate decisions are coordinated with tissue morphogenesis is poorly understood. Here we have examined ductal morphology, endocrine progenitor cell fate and Notch signaling in Ngn3−/− mice, which do not produce islet cells. Ngn3 deficiency results in reduced branching and enlarged pancreatic duct-like structures, concomitant with Ngn3 promoter activation throughout the ductal epithelium and reduced Notch signaling. Conversely, forced generation of surplus endocrine progenitor cells causes reduced duct caliber and an excessive number of tip cells. Thus, endocrine progenitor cells normally provide a feedback signal to adjacent multipotent ductal progenitor cells that activates Notch signaling, inhibits further endocrine differentiation and promotes proper morphogenesis. These results uncover a novel layer of regulation coordinating pancreas morphogenesis and endocrine/exocrine differentiation, and suggest ways to enhance the yield of beta-cells from stem cells. PMID:21888903

  16. Transmission of ranavirus between ectothermic vertebrate hosts.

    PubMed

    Brenes, Roberto; Gray, Matthew J; Waltzek, Thomas B; Wilkes, Rebecca P; Miller, Debra L

    2014-01-01

    Transmission is an essential process that contributes to the survival of pathogens. Ranaviruses are known to infect different classes of lower vertebrates including amphibians, fishes and reptiles. Differences in the likelihood of infection among ectothermic vertebrate hosts could explain the successful yearlong persistence of ranaviruses in aquatic environments. The goal of this study was to determine if transmission of a Frog Virus 3 (FV3)-like ranavirus was possible among three species from different ectothermic vertebrate classes: Cope's gray treefrog (Hyla chrysoscelis) larvae, mosquito fish (Gambusia affinis), and red-eared slider (Trachemys scripta elegans). We housed individuals previously exposed to the FV3-like ranavirus with naïve (unexposed) individuals in containers divided by plastic mesh screen to permit water flow between subjects. Our results showed that infected gray treefrog larvae were capable of transmitting ranavirus to naïve larval conspecifics and turtles (60% and 30% infection, respectively), but not to fish. Also, infected turtles and fish transmitted ranavirus to 50% and 10% of the naïve gray treefrog larvae, respectively. Nearly all infected amphibians experienced mortality, whereas infected turtles and fish did not die. Our results demonstrate that ranavirus can be transmitted through water among ectothermic vertebrate classes, which has not been reported previously. Moreover, fish and reptiles might serve as reservoirs for ranavirus given their ability to live with subclinical infections. Subclinical infections of ranavirus in fish and aquatic turtles could contribute to the pathogen's persistence, especially when highly susceptible hosts like amphibians are absent as a result of seasonal fluctuations in relative abundance.

  17. Light sensitivity in a vertebrate mechanoreceptor?

    PubMed Central

    Baker, Gary E.; de Grip, Willem J.; Turton, Michael; Wagner, Hans-Joachim; Foster, Russell G.; Douglas, Ron H.

    2015-01-01

    ABSTRACT Using immunohistochemistry and western blot analysis, we demonstrate that melanopsin is localised in cells around the central pore of lateral line neuromasts in the African clawed frog, Xenopus laevis. Since melanopsin is a known photoreceptor pigment with diverse functions in vertebrates, we suggest that the lateral line of Xenopus laevis, which is primarily a mechanoreceptor, might also be light sensitive. Potential functions of such photosensitivity are discussed, including its role in mediating locomotor responses following dermal illumination. PMID:26206352

  18. The Timing of Timezyme Diversification in Vertebrates

    PubMed Central

    Cazaméa-Catalan, Damien; Besseau, Laurence; Falcón, Jack; Magnanou, Elodie

    2014-01-01

    All biological functions in vertebrates are synchronized with daily and seasonal changes in the environment by the time keeping hormone melatonin. Its nocturnal surge is primarily due to the rhythmic activity of the arylalkylamine N-acetyl transferase AANAT, which thus became the focus of many investigations regarding its evolution and function. Various vertebrate isoforms have been reported from cartilaginous fish to mammals but their origin has not been clearly established. Using phylogeny and synteny, we took advantage of the increasing number of available genomes in order to test whether the various rounds of vertebrate whole genome duplications were responsible for the diversification of AANAT. We highlight a gene secondary loss of the AANAT2 in the Sarcopterygii, revealing for the first time that the AAANAT1/2 duplication occurred before the divergence between Actinopterygii (bony fish) and Sarcopterygii (tetrapods, lobe-finned fish, and lungfish). We hypothesize the teleost-specific whole genome duplication (WDG) generated the appearance of the AANAT1a/1b and the AANAT2/2′paralogs, the 2′ isoform being rapidly lost in the teleost common ancestor (ray-finned fish). We also demonstrate the secondary loss of the AANAT1a in a Paracantopterygii (Atlantic cod) and of the 1b in some Ostariophysi (zebrafish and cave fish). Salmonids present an even more diverse set of AANATs that may be due to their specific WGD followed by secondary losses. We propose that vertebrate AANAT diversity resulted from 3 rounds of WGD followed by previously uncharacterized secondary losses. Extant isoforms show subfunctionalized localizations, enzyme activities and affinities that have increased with time since their emergence. PMID:25486407

  19. The timing of Timezyme diversification in vertebrates.

    PubMed

    Cazaméa-Catalan, Damien; Besseau, Laurence; Falcón, Jack; Magnanou, Elodie

    2014-01-01

    All biological functions in vertebrates are synchronized with daily and seasonal changes in the environment by the time keeping hormone melatonin. Its nocturnal surge is primarily due to the rhythmic activity of the arylalkylamine N-acetyl transferase AANAT, which thus became the focus of many investigations regarding its evolution and function. Various vertebrate isoforms have been reported from cartilaginous fish to mammals but their origin has not been clearly established. Using phylogeny and synteny, we took advantage of the increasing number of available genomes in order to test whether the various rounds of vertebrate whole genome duplications were responsible for the diversification of AANAT. We highlight a gene secondary loss of the AANAT2 in the Sarcopterygii, revealing for the first time that the AAANAT1/2 duplication occurred before the divergence between Actinopterygii (bony fish) and Sarcopterygii (tetrapods, lobe-finned fish, and lungfish). We hypothesize the teleost-specific whole genome duplication (WDG) generated the appearance of the AANAT1a/1b and the AANAT2/2'paralogs, the 2' isoform being rapidly lost in the teleost common ancestor (ray-finned fish). We also demonstrate the secondary loss of the AANAT1a in a Paracantopterygii (Atlantic cod) and of the 1b in some Ostariophysi (zebrafish and cave fish). Salmonids present an even more diverse set of AANATs that may be due to their specific WGD followed by secondary losses. We propose that vertebrate AANAT diversity resulted from 3 rounds of WGD followed by previously uncharacterized secondary losses. Extant isoforms show subfunctionalized localizations, enzyme activities and affinities that have increased with time since their emergence. PMID:25486407

  20. The immunoglobulins of cold-blooded vertebrates.

    PubMed

    Pettinello, Rita; Dooley, Helen

    2014-11-24

    Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more "conventional" mammalian species.

  1. The molecular biology of vertebrate olfaction.

    PubMed

    Hayden, Sara; Teeling, Emma C

    2014-11-01

    The importance of chemosensation for vertebrates is reflected in the vast and variable nature of their chemosensory tissues, neurons, and genes, which we explore in this review. Immense progress has been made in elucidating the molecular biology of olfaction since the discovery of the olfactory receptor genes by Buck and Axel, which eventually won the authors the Nobel Prize. In particular, research linking odor ligands to olfactory receptors (ORs) is truly revolutionizing our understanding of how a large but limited number of chemosensory receptors can allow us to perceive the massive diversity of odors in our habitat. This research is providing insight into the evolution of genomes and providing the raw data needed to explore links between genotype and phenotype, still a grand challenge in biology. Research into olfaction is still developing and will no doubt continue until we have a clear understanding of how all odors are detected and the evolutionary forces that have molded the chemosensory subgenome in vertebrates. This knowledge will not only be a huge step in elucidating olfactory function, advancing scientific knowledge and techniques, but there are also commercial applications for this research. This review focuses on the molecular basis of chemosensation, particularly olfaction, its evolution across vertebrates and the recent molecular advances linking odors to their cognate receptors. PMID:25312375

  2. Flapping wing aerodynamics: from insects to vertebrates.

    PubMed

    Chin, Diana D; Lentink, David

    2016-04-01

    More than a million insects and approximately 11,000 vertebrates utilize flapping wings to fly. However, flapping flight has only been studied in a few of these species, so many challenges remain in understanding this form of locomotion. Five key aerodynamic mechanisms have been identified for insect flight. Among these is the leading edge vortex, which is a convergent solution to avoid stall for insects, bats and birds. The roles of the other mechanisms - added mass, clap and fling, rotational circulation and wing-wake interactions - have not yet been thoroughly studied in the context of vertebrate flight. Further challenges to understanding bat and bird flight are posed by the complex, dynamic wing morphologies of these species and the more turbulent airflow generated by their wings compared with that observed during insect flight. Nevertheless, three dimensionless numbers that combine key flow, morphological and kinematic parameters - the Reynolds number, Rossby number and advance ratio - govern flapping wing aerodynamics for both insects and vertebrates. These numbers can thus be used to organize an integrative framework for studying and comparing animal flapping flight. Here, we provide a roadmap for developing such a framework, highlighting the aerodynamic mechanisms that remain to be quantified and compared across species. Ultimately, incorporating complex flight maneuvers, environmental effects and developmental stages into this framework will also be essential to advancing our understanding of the biomechanics, movement ecology and evolution of animal flight. PMID:27030773

  3. Effects of hypoxia on vertebrate blood vessels.

    PubMed

    Russell, Michael J; Dombkowski, Ryan A; Olson, Kenneth R

    2008-03-01

    Hypoxia contracts mammalian respiratory vessels and increases vascular resistance in respiratory tissues of many vertebrates. In systemic vessels these responses vary, hypoxia relaxes mammalian vessels and contracts systemic arteries from cyclostomes. It has been proposed that hypoxic vasoconstriction in cyclostome systemic arteries is the antecedent to mammalian hypoxic pulmonary vasoconstriction, however, phylogenetic characterization of hypoxic responses is lacking. In this study, we characterized the hypoxic response of isolated systemic and respiratory vessels from a variety of vertebrates using standard myography. Pre-gill/respiratory (ventral aorta, afferent branchial artery, pulmonary artery) and post-gill/systemic (dorsal and thoracic aortas, efferent branchial artery) from lamprey (Petromyzon marinus), sandbar shark (Carcharhinus plumbeus), yellowfin tuna (Thunnus albacares), American bullfrog (Rana catesbeiana), American alligator (Alligator mississippiensis), Pekin duck (Anas platyrhynchos domesticus), chicken (Gallus domesticus) and rat (Rattus norvegicus) were exposed to hypoxia at rest or during pre-stimulation (elevated extracellular potassium, epinephrine or norepinephrine). Hypoxia produced a relaxation or transient contraction followed by relaxation in all pre-gill vessels, except for contraction in lamprey, and vasoconstriction or tri-phasic constriction-dilation-constriction in all pulmonary vessels. Hypoxia contracted systemic vessels from all animals except shark and rat and in pre-contracted rat aortas it produced a transient contraction followed by relaxation. These results show that while the classic "systemic hypoxic vasodilation and pulmonary hypoxic vasoconstriction" may occur in the microcirculation, the hypoxic response of the vertebrate macrocirculation is quite variable. These findings also suggest that hypoxic vasoconstriction is a phylogenetically ancient response. PMID:18214862

  4. BK Channels in the Vertebrate Inner Ear.

    PubMed

    Pyott, S J; Duncan, R K

    2016-01-01

    The perception of complex acoustic stimuli begins with the deconstruction of sound into its frequency components. This spectral processing occurs first and foremost in the inner ear. In vertebrates, two very different strategies of frequency analysis have evolved. In nonmammalian vertebrates, the sensory hair cells of the inner ear are intrinsically electrically tuned to a narrow band of acoustic frequencies. This electrical tuning relies on the interplay between BK channels and voltage-gated calcium channels. Systematic variations in BK channel density and kinetics establish a gradient in electrical resonance that enables the coding of a broad range of acoustic frequencies. In contrast, mammalian hair cells are extrinsically tuned by mechanical properties of the cochlear duct. Even so, mammalian hair cells also express BK channels. These BK channels play critical roles in various aspects of mammalian auditory signaling, from developmental maturation to protection against acoustic trauma. This review summarizes the anatomical localization, biophysical properties, and functional contributions of BK channels in vertebrate inner ears. Areas of future research, based on an updated understanding of the biology of both BK channels and the inner ear, are also highlighted. Investigation of BK channels in the inner ear continues to provide fertile research grounds for examining both BK channel biophysics and the molecular mechanisms underlying signal processing in the auditory periphery. PMID:27238269

  5. The immunoglobulins of cold-blooded vertebrates.

    PubMed

    Pettinello, Rita; Dooley, Helen

    2014-01-01

    Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more "conventional" mammalian species. PMID:25427250

  6. T-cell receptors in ectothermic vertebrates.

    PubMed

    Charlemagne, J; Fellah, J S; De Guerra, A; Kerfourn, F; Partula, S

    1998-12-01

    The structure and expression of genes encoding molecules homologous to mammalian T-cell receptors (TCR) have been recently studied in ectothermic vertebrate species representative of chondrychthians, teleosts, and amphibians. The overall TCR chain structure is well conserved in phylogeny: TCR beta- and TCR alpha-like chains were detected in all the species analyzed; TCR gamma- and TCR delta-like chains were also present in a chondrychthian species. The diversity potential of the variable (V) and joining (J) segments is rather large and, as in mammals, conserved diversity (D) segments are associated to the TCR beta and TCR delta chains. An important level of junctional diversity occurred at the V-(D)-J junctions, with the potential addition of N- and P-nucleotides. Thus, the conservation of the structure and of the potential of diversity of TCR molecules have been under a permanent selective pressure during vertebrate evolution. The structure of MHC class I and class II molecules was also well conserved in jawed vertebrates. TCR and MHC molecules are strongly functionally linked and play a determinant role in the initiation and the regulation of the specific immune responses; thus, it is not surprising that their structures have been reciprocally frozen during evolution. PMID:9914905

  7. Nestedness of Ectoparasite-Vertebrate Host Networks

    PubMed Central

    Graham, Sean P.; Hassan, Hassan K.; Burkett-Cadena, Nathan D.; Guyer, Craig; Unnasch, Thomas R.

    2009-01-01

    Determining the structure of ectoparasite-host networks will enable disease ecologists to better understand and predict the spread of vector-borne diseases. If these networks have consistent properties, then studying the structure of well-understood networks could lead to extrapolation of these properties to others, including those that support emerging pathogens. Borrowing a quantitative measure of network structure from studies of mutualistic relationships between plants and their pollinators, we analyzed 29 ectoparasite-vertebrate host networks—including three derived from molecular bloodmeal analysis of mosquito feeding patterns—using measures of nestedness to identify non-random interactions among species. We found significant nestedness in ectoparasite-vertebrate host lists for habitats ranging from tropical rainforests to polar environments. These networks showed non-random patterns of nesting, and did not differ significantly from published estimates of nestedness from mutualistic networks. Mutualistic and antagonistic networks appear to be organized similarly, with generalized ectoparasites interacting with hosts that attract many ectoparasites and more specialized ectoparasites usually interacting with these same “generalized” hosts. This finding has implications for understanding the network dynamics of vector-born pathogens. We suggest that nestedness (rather than random ectoparasite-host associations) can allow rapid transfer of pathogens throughout a network, and expand upon such concepts as the dilution effect, bridge vectors, and host switching in the context of nested ectoparasite-vertebrate host networks. PMID:19924299

  8. Fungal osteomyelitis with vertebral re-ossification

    PubMed Central

    O′Guinn, Devon J.; Serletis, Demitre; Kazemi, Noojan

    2015-01-01

    Introduction We present a rare case of thoracic vertebral osteomyelitis secondary to pulmonary Blastomyces dermatitides. Presentation of case A 27-year-old male presented with three months of chest pains and non-productive cough. Examination revealed diminished breath sounds on the right. CT/MR imaging confirmed a right-sided pre-/paravertebral soft tissue mass and destructive lytic lesions from T2 to T6. CT-guided needle biopsy confirmed granulomatous pulmonary Blastomycosis. Conservative management with antifungal therapy was initiated. Neurosurgical review confirmed no clinical or profound radiographic instability, and the patient was stabilized with TLSO bracing. Serial imaging 3 months later revealed near-resolution of the thoracic soft tissue mass, with vertebral re-ossification from T2 to T6. Discussion Fungal osteomyelitis presents a rare entity in the spectrum of spinal infections. In such cases, lytic spinal lesions are classically seen in association with a large paraspinous mass. Fungal infections of the spinal column may be treated conservatively, with surgical intervention reserved for progressive cases manifesting with neurological compromise and/or spinal column instability. Here, we found unexpected evidence for vertebral re-ossification across the affected thoracic levels (T2-6) in response to IV antibiotic therapy and conservative bracing, nearly 3 months later. PMID:26692163

  9. Flapping wing aerodynamics: from insects to vertebrates.

    PubMed

    Chin, Diana D; Lentink, David

    2016-04-01

    More than a million insects and approximately 11,000 vertebrates utilize flapping wings to fly. However, flapping flight has only been studied in a few of these species, so many challenges remain in understanding this form of locomotion. Five key aerodynamic mechanisms have been identified for insect flight. Among these is the leading edge vortex, which is a convergent solution to avoid stall for insects, bats and birds. The roles of the other mechanisms - added mass, clap and fling, rotational circulation and wing-wake interactions - have not yet been thoroughly studied in the context of vertebrate flight. Further challenges to understanding bat and bird flight are posed by the complex, dynamic wing morphologies of these species and the more turbulent airflow generated by their wings compared with that observed during insect flight. Nevertheless, three dimensionless numbers that combine key flow, morphological and kinematic parameters - the Reynolds number, Rossby number and advance ratio - govern flapping wing aerodynamics for both insects and vertebrates. These numbers can thus be used to organize an integrative framework for studying and comparing animal flapping flight. Here, we provide a roadmap for developing such a framework, highlighting the aerodynamic mechanisms that remain to be quantified and compared across species. Ultimately, incorporating complex flight maneuvers, environmental effects and developmental stages into this framework will also be essential to advancing our understanding of the biomechanics, movement ecology and evolution of animal flight.

  10. The Immunoglobulins of Cold-Blooded Vertebrates

    PubMed Central

    Pettinello, Rita; Dooley, Helen

    2014-01-01

    Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more “conventional” mammalian species. PMID:25427250

  11. The molecular biology of vertebrate olfaction.

    PubMed

    Hayden, Sara; Teeling, Emma C

    2014-11-01

    The importance of chemosensation for vertebrates is reflected in the vast and variable nature of their chemosensory tissues, neurons, and genes, which we explore in this review. Immense progress has been made in elucidating the molecular biology of olfaction since the discovery of the olfactory receptor genes by Buck and Axel, which eventually won the authors the Nobel Prize. In particular, research linking odor ligands to olfactory receptors (ORs) is truly revolutionizing our understanding of how a large but limited number of chemosensory receptors can allow us to perceive the massive diversity of odors in our habitat. This research is providing insight into the evolution of genomes and providing the raw data needed to explore links between genotype and phenotype, still a grand challenge in biology. Research into olfaction is still developing and will no doubt continue until we have a clear understanding of how all odors are detected and the evolutionary forces that have molded the chemosensory subgenome in vertebrates. This knowledge will not only be a huge step in elucidating olfactory function, advancing scientific knowledge and techniques, but there are also commercial applications for this research. This review focuses on the molecular basis of chemosensation, particularly olfaction, its evolution across vertebrates and the recent molecular advances linking odors to their cognate receptors.

  12. Role of morphogens in brain growth.

    PubMed

    Tannahill, David; Harris, Laura W; Keynes, Roger

    2005-09-15

    During the last century, experiments on the chick embryo established that the ballooning expansion of the early forebrain and midbrain vesicles is dependent on the underlying axial (notochordal) mesoderm. Transient separation of the early midbrain primordium from the notochord causes subsequent collapse of both midbrain and forebrain (telencephalic) vesicles, accompanied by pronounced folding of the neural epithelium. More recent experiments have shown that vesicle collapse is caused by defective Sonic Hedgehog (Shh) signaling from the notochord and floor plate. Separation of the notochord from the brain causes loss of ventral Shh expression, resulting in reduced cell proliferation and increased cell death in the expanding neural epithelium, and culminating in vesicle collapse. These experiments are reviewed here, and set in the context of other studies illustrating the wide range of molecular and cellular processes that cause abnormal brain morphogenesis when perturbed. We also speculate that variation in the regulation of signaling pathways such as Hedgehog may have played a significant part in generating rapid morphogenetic changes during the evolution of the vertebrate brain.

  13. FRAX and the effect of teriparatide on vertebral and non-vertebral fracture

    PubMed Central

    Harvey, Nicholas C; Kanis, John A; Odén, Anders; Burge, Russel T; Mitlak, Bruce H; Johansson, Helena; McCloskey, Eugene V

    2016-01-01

    Summary Daily teriparatide injections have been shown to reduce vertebral and non-vertebral fractures. Here we demonstrate that the magnitude of fracture risk reduction is independent of baseline fracture probability assessed by FRAX. Background Daily administration of 20μg or 40μg teriparatide has been shown to significantly decrease the risk of vertebral and non-vertebral fracture compared with placebo. The aim of the present study was to evaluate fracture risk assessed at baseline using the FRAX® tool and to determine the efficacy of teriparatide as a function of baseline fracture risk. Methods 1637 postmenopausal women in the pivotal phase 3 trial, randomly assigned to receive placebo (n=544), teriparatide 20 μg per day (n=541) or teriparatide 40 μg per day (n=552), were studied. Baseline clinical risk factors were entered into country-specific FRAX models to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. Because there was no difference in effect of 20 and 40μg teriparatide daily on fracture occurrence, the two active groups were merged. The interaction between probability of a major fracture and treatment efficacy was examined by Poisson regression. Results The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.2-67.2%. Treatment with teriparatide was associated with a 37% decrease in all non-vertebral fractures (95% CI:10-56 %) and a 56% decrease in low energy non-vertebral fractures (95% CI:24-75%) compared with placebo. The risk of morphometric vertebral fractures decreased significantly by 66% (95% CI:50-77%). Hazard ratios for the effect of teriparatide on the fracture outcome did not change significantly with increasing fracture probability (p>0.30). Similar findings were noted for the interaction when BMD was excluded from the FRAX model, or when probability of hip fracture was used as the marker of baseline risk. Conclusion We conclude that teriparatide

  14. Plant Growth and Morphogenesis under Different Gravity Conditions: Relevance to Plant Life in Space.

    PubMed

    Hoson, Takayuki

    2014-05-16

    The growth and morphogenesis of plants are entirely dependent on the gravitational acceleration of earth. Under microgravity conditions in space, these processes are greatly modified. Recent space experiments, in combination with ground-based studies, have shown that elongation growth is stimulated and lateral expansion suppressed in various shoot organs and roots under microgravity conditions. Plant organs also show automorphogenesis in space, which consists of altered growth direction and spontaneous curvature in the dorsiventral (back and front) directions. Changes in cell wall properties are responsible for these modifications of growth and morphogenesis under microgravity conditions. Plants live in space with interesting new sizes and forms.

  15. Morphogenesis in Plants: Modeling the Shoot Apical Meristem, and Possible Applications

    NASA Technical Reports Server (NTRS)

    Mjolsness, Eric; Gor, Victoria; Meyerowitz, Elliot; Mann, Tobias

    1998-01-01

    A key determinant of overall morphogenesis in flowering plants such as Arabidopsis thaliana is the shoot apical meristem (growing tip of a shoot). Gene regulation networks can be used to model this system. We exhibit a very preliminary two-dimensional model including gene regulation and intercellular signaling, but omitting cell division and dynamical geometry. The model can be trained to have three stable regions of gene expression corresponding to the central zone, peripheral zone, and rib meristem. We also discuss a space-engineering motivation for studying and controlling the morphogenesis of plants using such computational models.

  16. Virulence-specific cell cycle and morphogenesis connections in pathogenic fungi.

    PubMed

    Pérez-Martín, José; Bardetti, Paola; Castanheira, Sónia; de la Torre, Antonio; Tenorio-Gómez, María

    2016-09-01

    To initiate pathogenic development, pathogenic fungi respond to a set of inductive cues. Some of them are of an extracellular nature (environmental signals), while others are intracellular (developmental signals). These signals must be integrated into a single response whose major outcome is changes in the morphogenesis of the fungus. The regulation of the cell cycle is pivotal during these cellular differentiation steps; therefore, cell cycle regulation would likely provide control points for infectious development by fungal pathogens. Here, we provide clues to understanding how the control of the cell cycle is integrated with the morphogenesis program in pathogenic fungi, and we review current examples that support these connections. PMID:27032479

  17. [Effect of colchicine on the morphogenesis and ultrastruct of Acetabularia mediterranea].

    PubMed

    Betina, M I; Salamakha, O V; Tikhomirova, L A; Ianushevich, I V

    1977-01-01

    The effect of colchicine on morphogenesis of the regenerating nuclear fragments of Acetabularia mediterranea has been studied. Colchicine was shown to inhibit the formation of caps. The algae are most sensitive to colchicine at the early stages of regeneration. The breakdown of microtubules in the perinuclear cytoplasm of regenerating algae under the effect of colchicine was found under the electron microscopy. The breakdown of microtubules in this zone appears not to disturb the transport of morphogenetical substances in the apical cell part. Colchicine inhibits the morphogenesis, apparently, at the expense of protein inactivation in the zone of growth.

  18. Surgical treatment of aggressive vertebral hemangiomas.

    PubMed

    Vasudeva, Viren S; Chi, John H; Groff, Michael W

    2016-08-01

    OBJECTIVE Vertebral hemangiomas are common tumors that are benign and generally asymptomatic. Occasionally these lesions can exhibit aggressive features such as bony expansion and erosion into the epidural space resulting in neurological symptoms. Surgery is often recommended in these cases, especially if symptoms are severe or rapidly progressive. Some surgeons perform decompression alone, others perform gross-total resection, while others perform en bloc resection. Radiation, embolization, vertebroplasty, and ethanol injection have also been used in combination with surgery. Despite the variety of available treatment options, the optimal management strategy is unclear because aggressive vertebral hemangiomas are uncommon lesions, making it difficult to perform large trials. For this reason, the authors chose instead to report their institutional experience along with a comprehensive review of the literature. METHODS A departmental database was searched for patients with a pathological diagnosis of "hemangioma" between 2008 and 2015. Medical records were reviewed to identify patients with aggressive vertebral hemangiomas, and these cases were reviewed in detail. RESULTS Five patients were identified who underwent surgery for treatment of aggressive vertebral hemangiomas during the specified time period. There were 2 lumbar and 3 thoracic lesions. One patient underwent en bloc spondylectomy, 2 patients had piecemeal gross-total resection, and the remaining 2 had subtotal tumor resection. Intraoperative vertebroplasty was used in 3 cases to augment the anterior column or to obliterate residual tumor. Adjuvant radiation was used in 1 case where there was residual tumor as well. The patient who underwent en bloc spondylectomy experienced several postoperative complications requiring additional medical care and reoperation. At an average follow-up of 31 months (range 3-65 months), no patient had any recurrence of disease and all were clinically asymptomatic, except the

  19. Surgical treatment of aggressive vertebral hemangiomas.

    PubMed

    Vasudeva, Viren S; Chi, John H; Groff, Michael W

    2016-08-01

    OBJECTIVE Vertebral hemangiomas are common tumors that are benign and generally asymptomatic. Occasionally these lesions can exhibit aggressive features such as bony expansion and erosion into the epidural space resulting in neurological symptoms. Surgery is often recommended in these cases, especially if symptoms are severe or rapidly progressive. Some surgeons perform decompression alone, others perform gross-total resection, while others perform en bloc resection. Radiation, embolization, vertebroplasty, and ethanol injection have also been used in combination with surgery. Despite the variety of available treatment options, the optimal management strategy is unclear because aggressive vertebral hemangiomas are uncommon lesions, making it difficult to perform large trials. For this reason, the authors chose instead to report their institutional experience along with a comprehensive review of the literature. METHODS A departmental database was searched for patients with a pathological diagnosis of "hemangioma" between 2008 and 2015. Medical records were reviewed to identify patients with aggressive vertebral hemangiomas, and these cases were reviewed in detail. RESULTS Five patients were identified who underwent surgery for treatment of aggressive vertebral hemangiomas during the specified time period. There were 2 lumbar and 3 thoracic lesions. One patient underwent en bloc spondylectomy, 2 patients had piecemeal gross-total resection, and the remaining 2 had subtotal tumor resection. Intraoperative vertebroplasty was used in 3 cases to augment the anterior column or to obliterate residual tumor. Adjuvant radiation was used in 1 case where there was residual tumor as well. The patient who underwent en bloc spondylectomy experienced several postoperative complications requiring additional medical care and reoperation. At an average follow-up of 31 months (range 3-65 months), no patient had any recurrence of disease and all were clinically asymptomatic, except the

  20. A Classification System for the Spread of Polymethyl Methacrylate in Vertebral Bodies Treated with Vertebral Augmentation

    PubMed Central

    Frankl, Joseph; Sakata, Michael P.; Choudhary, Gagandeep; Hur, Seung; Peterson, Andrew; Hennemeyer, Charles T.

    2016-01-01

    In this study, we develop a classification system for describing polymethyl methacrylate (PMMA) spread in vertebral bodies after kyphoplasty or vertebroplasty for vertebral compression fractures (VCFs) and for assessing whether PMMA spread varies between operators, VCF etiology, or vertebral level. Intraoperative fluoroscopic images of 198 vertebral levels were reviewed in 137 patients (women, 84; men, 53; mean age, 75.8 ± 12.5; and those with a diagnosis of osteoporosis, 63%) treated with kyphoplasty between January 01, 2015 and May 31, 2015 at a single center to create a 5-class descriptive system. PMMA spread patterns in the same images were then classified by 2 board-certified radiologists, and a third board-certified radiologist resolved conflicts. A total of 2 primary PMMA spread patterns were identified, namely, acinar and globular, with subtypes of localized acinar, diffuse globular, and mixed, to describe an equal combination of patterns. Interrater reliability using the system was moderate (κ = 0.47). After resolving conflicts, the most common spread class was globular (n = 63), followed by mixed (n = 58), diffuse globular (n = 30), acinar (n = 27), and localized acinar (n = 20). The spread class after treatment by the 2 most frequent operators differed significantly (n1 = 63, n2 = 70; P < .0001). There was no difference in the spread class between VCF etiologies or vertebral levels. PMMA spread may, therefore, be a modifiable parameter that affects kyphoplasty and vertebroplasty efficacy and adverse events. PMID:27795998

  1. Bcl-wav and the mitochondrial calcium uniporter drive gastrula morphogenesis in zebrafish.

    PubMed

    Prudent, Julien; Popgeorgiev, Nikolay; Bonneau, Benjamin; Thibaut, Julien; Gadet, Rudy; Lopez, Jonathan; Gonzalo, Philippe; Rimokh, Ruth; Manon, Stephen; Houart, Corinne; Herbomel, Philippe; Aouacheria, Abdel; Gillet, Germain

    2013-01-01

    Bcl-2 proteins are acknowledged as key regulators of programmed cell death. However, increasing data suggest additional roles, including regulation of the cell cycle, metabolism and cytoskeletal dynamics. Here we report the discovery and characterization of a new Bcl-2-related multidomain apoptosis accelerator, Bcl-wav, found in fish and frogs. Genetic and molecular studies in zebrafish indicate that Bcl-wav and the recently identified mitochondrial calcium uniporter (MCU) contribute to the formation of the notochord axis by controlling blastomere convergence and extension movements during gastrulation. Furthermore, we found that Bcl-wav controls intracellular Ca(2+) trafficking by acting on the mitochondrial voltage-dependent anion channel, and possibly on MCU, with direct consequences on actin microfilament dynamics and blastomere migration guidance. Thus, from an evolutionary point of view, the original function of Bcl-2 proteins might have been to contribute in controlling the global positioning system of blastomeres during gastrulation, a critical step in metazoan development.

  2. Bcl-wav and the mitochondrial calcium uniporter drive gastrula morphogenesis in zebrafish.

    PubMed

    Prudent, Julien; Popgeorgiev, Nikolay; Bonneau, Benjamin; Thibaut, Julien; Gadet, Rudy; Lopez, Jonathan; Gonzalo, Philippe; Rimokh, Ruth; Manon, Stephen; Houart, Corinne; Herbomel, Philippe; Aouacheria, Abdel; Gillet, Germain

    2013-01-01

    Bcl-2 proteins are acknowledged as key regulators of programmed cell death. However, increasing data suggest additional roles, including regulation of the cell cycle, metabolism and cytoskeletal dynamics. Here we report the discovery and characterization of a new Bcl-2-related multidomain apoptosis accelerator, Bcl-wav, found in fish and frogs. Genetic and molecular studies in zebrafish indicate that Bcl-wav and the recently identified mitochondrial calcium uniporter (MCU) contribute to the formation of the notochord axis by controlling blastomere convergence and extension movements during gastrulation. Furthermore, we found that Bcl-wav controls intracellular Ca(2+) trafficking by acting on the mitochondrial voltage-dependent anion channel, and possibly on MCU, with direct consequences on actin microfilament dynamics and blastomere migration guidance. Thus, from an evolutionary point of view, the original function of Bcl-2 proteins might have been to contribute in controlling the global positioning system of blastomeres during gastrulation, a critical step in metazoan development. PMID:23942336

  3. MAB21L2, a vertebrate member of the Male-abnormal 21 family, modulates BMP signaling and interacts with SMAD1

    PubMed Central

    Baldessari, Danila; Badaloni, Aurora; Longhi, Renato; Zappavigna, Vincenzo; Consalez, G Giacomo

    2004-01-01

    Background Through in vivo loss-of-function studies, vertebrate members of the Male abnormal 21 (mab-21) gene family have been implicated in gastrulation, neural tube formation and eye morphogenesis. Despite mounting evidence of their considerable importance in development, the biochemical properties and nature of MAB-21 proteins have remained strikingly elusive. In addition, genetic studies conducted in C. elegans have established that in double mutants mab-21 is epistatic to genes encoding various members of a Transforming Growth Factor beta (TGF-beta) signaling pathway involved in the formation of male-specific sensory organs. Results Through a gain-of-function approach, we analyze the interaction of Mab21l2 with a TGF-beta signaling pathway in early vertebrate development. We show that the vertebrate mab-21 homolog Mab21l2 antagonizes the effects of Bone Morphogenetic Protein 4 (BMP4) overexpression in vivo, rescuing the dorsal axis and restoring wild-type distribution of Chordin and Xvent2 transcripts in Xenopus gastrulae. We show that MAB21L2 immunoprecipitates in vivo with the BMP4 effector SMAD1, whilst in vitro it binds SMAD1 and the SMAD1-SMAD4 complex. Finally, when targeted to an heterologous promoter, MAB21L2 acts as a transcriptional repressor. Conclusions Our results provide the first biochemical and cellular foundation for future functional studies of mab-21 genes in normal neural development and its pathological disturbances. PMID:15613244

  4. Vertebrate MitBASE: a specialised database on vertebrate mitochondrial DNA sequences.

    PubMed

    Carone, A; Malladi, S B; Attimonelli, M; Saccone, C

    1999-01-01

    Vertebrate MitBASE is a specialized database where all the vertebrate mitochondrial DNA entries from primary databases are collected, revised and integrated with new information emerging from the literature. Variant sequences are also analyzed, aligned and linked to reference sequences. Data related to the same species and fragment can be viewed over the WWW. The database has a flexible interface and a retrieval system to help non-expert users and contains information not currently available in the primary databases. Vertebrate MitBASE is now available through the MitBASE home page at URL: http://www.ebi.ac.uk/htbin/Mitbase/mitb ase.pl. This work is part of a larger project, MitBASE which is a network of databases covering the full panorama of knowledge on mitochondrial DNA from protists to human sequences.

  5. Early Bone Marrow Edema Pattern of the Osteoporotic Vertebral Compression Fracture : Can Be Predictor of Vertebral Deformity Types and Prognosis?

    PubMed Central

    Ahn, Sung Eun; Park, Ji Seon; Jin, Wook; Park, So Young; Kim, Sung Bum

    2016-01-01

    Objective To evaluate whether an early bone marrow edema pattern predicts vertebral deformity types and prognosis in osteoporotic vertebral compression fracture (OVCF). Methods This retrospective study enrolled 64 patients with 75 acute OVCFs who underwent early MRI and followed up MRI. On early MRI, the low SI pattern of OVCF on T1WI were assessed and classified into 3 types (diffuse, globular or patchy, band-like). On followed up MRI, the vertebral deformity types (anterior wedge, biconcave, crush), degree of vertebral body height loss, incidence of vertebral osteonecrosis and spinal stenosis were assessed for each vertebral fracture types. Results According to the early bone marrow edema pattern on T1WI, 26 vertebrae were type 1, 14 vertebrae were type 2 and 35 vertebrae were type 3. On followed up MRI, the crush-type vertebral deformity was most frequent among the type 1 OVCFs, the biconcave-type vertebral deformity was most frequent among the type 2 OVCFs and the anterior wedge-type vertebral deformity was most frequent among the type 3 OVCFs (p<0.001). In addition, type 1 early bone marrow edema pattern of OVCF on T1WI were associated with higher incidence of severe degree vertebral body height loss, vertebral osteonecrosis and spinal stenosis on the follow up MRI. Conclusion Early bone marrow edema pattern of OVCF on T1WI, significant correlated with vertebral deformity types on the follow up MRI. The severe degree of vertebral height loss, vertebral osteonecrosis, and spinal stenosis were more frequent in patients with diffuse low SI pattern. PMID:26962419

  6. Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone.

    PubMed

    van de Ven, Cesca; Bialecka, Monika; Neijts, Roel; Young, Teddy; Rowland, Jennifer E; Stringer, Emma J; Van Rooijen, Carina; Meijlink, Frits; Nóvoa, Ana; Freund, Jean-Noel; Mallo, Moises; Beck, Felix; Deschamps, Jacqueline

    2011-08-01

    Decrease in Cdx dosage in an allelic series of mouse Cdx mutants leads to progressively more severe posterior vertebral defects. These defects are corrected by posterior gain of function of the Wnt effector Lef1. Precocious expression of Hox paralogous 13 genes also induces vertebral axis truncation by antagonizing Cdx function. We report here that the phenotypic similarity also applies to patterning of the caudal neural tube and uro-rectal tracts in Cdx and Wnt3a mutants, and in embryos precociously expressing Hox13 genes. Cdx2 inactivation after placentation leads to posterior defects, including incomplete uro-rectal septation. Compound mutants carrying one active Cdx2 allele in the Cdx4-null background (Cdx2/4), transgenic embryos precociously expressing Hox13 genes and a novel Wnt3a hypomorph mutant all manifest a comparable phenotype with similar uro-rectal defects. Phenotype and transcriptome analysis in early Cdx mutants, genetic rescue experiments and gene expression studies lead us to propose that Cdx transcription factors act via Wnt signaling during the laying down of uro-rectal mesoderm, and that they are operative in an early phase of these events, at the site of tissue progenitors in the posterior growth zone of the embryo. Cdx and Wnt mutations and premature Hox13 expression also cause similar neural dysmorphology, including ectopic neural structures that sometimes lead to neural tube splitting at caudal axial levels. These findings involve the Cdx genes, canonical Wnt signaling and the temporal control of posterior Hox gene expression in posterior morphogenesis in the different embryonic germ layers. They shed a new light on the etiology of the caudal dysplasia or caudal regression range of human congenital defects.

  7. Evolution of Vertebrate Phototransduction: Cascade Activation

    PubMed Central

    Lamb, Trevor D.; Patel, Hardip; Chuah, Aaron; Natoli, Riccardo C.; Davies, Wayne I. L.; Hart, Nathan S.; Collin, Shaun P.; Hunt, David M.

    2016-01-01

    We applied high-throughput sequencing to eye tissue from several species of basal vertebrates (a hagfish, two species of lamprey, and five species of gnathostome fish), and we analyzed the mRNA sequences for the proteins underlying activation of the phototransduction cascade. The molecular phylogenies that we constructed from these sequences are consistent with the 2R WGD model of two rounds of whole genome duplication. Our analysis suggests that agnathans retain an additional representative (that has been lost in gnathostomes) in each of the gene families we studied; the evidence is strong for the G-protein α subunit (GNAT) and the cGMP phosphodiesterase (PDE6), and indicative for the cyclic nucleotide-gated channels (CNGA and CNGB). Two of the species (the hagfish Eptatretus cirrhatus and the lamprey Mordacia mordax) possess only a single class of photoreceptor, simplifying deductions about the composition of cascade protein isoforms utilized in their photoreceptors. For the other lamprey, Geotria australis, analysis of the ratios of transcript levels in downstream and upstream migrant animals permits tentative conclusions to be drawn about the isoforms used in four of the five spectral classes of photoreceptor. Overall, our results suggest that agnathan rod-like photoreceptors utilize the same GNAT1 as gnathostomes, together with a homodimeric PDE6 that may be agnathan-specific, whereas agnathan cone-like photoreceptors utilize a GNAT that may be agnathan-specific, together with the same PDE6C as gnathostomes. These findings help elucidate the evolution of the vertebrate phototransduction cascade from an ancestral chordate phototransduction cascade that existed prior to the vertebrate radiation. PMID:27189541

  8. Evolution of Vertebrate Phototransduction: Cascade Activation.

    PubMed

    Lamb, Trevor D; Patel, Hardip; Chuah, Aaron; Natoli, Riccardo C; Davies, Wayne I L; Hart, Nathan S; Collin, Shaun P; Hunt, David M

    2016-08-01

    We applied high-throughput sequencing to eye tissue from several species of basal vertebrates (a hagfish, two species of lamprey, and five species of gnathostome fish), and we analyzed the mRNA sequences for the proteins underlying activation of the phototransduction cascade. The molecular phylogenies that we constructed from these sequences are consistent with the 2R WGD model of two rounds of whole genome duplication. Our analysis suggests that agnathans retain an additional representative (that has been lost in gnathostomes) in each of the gene families we studied; the evidence is strong for the G-protein α subunit (GNAT) and the cGMP phosphodiesterase (PDE6), and indicative for the cyclic nucleotide-gated channels (CNGA and CNGB). Two of the species (the hagfish Eptatretus cirrhatus and the lamprey Mordacia mordax) possess only a single class of photoreceptor, simplifying deductions about the composition of cascade protein isoforms utilized in their photoreceptors. For the other lamprey, Geotria australis, analysis of the ratios of transcript levels in downstream and upstream migrant animals permits tentative conclusions to be drawn about the isoforms used in four of the five spectral classes of photoreceptor. Overall, our results suggest that agnathan rod-like photoreceptors utilize the same GNAT1 as gnathostomes, together with a homodimeric PDE6 that may be agnathan-specific, whereas agnathan cone-like photoreceptors utilize a GNAT that may be agnathan-specific, together with the same PDE6C as gnathostomes. These findings help elucidate the evolution of the vertebrate phototransduction cascade from an ancestral chordate phototransduction cascade that existed prior to the vertebrate radiation. PMID:27189541

  9. DEVELOPMENTAL PALEOBIOLOGY OF THE VERTEBRATE SKELETON

    PubMed Central

    RÜCKLIN, MARTIN; DONOGHUE, PHILIP C. J.; CUNNINGHAM, JOHN A.; MARONE, FEDERICA; STAMPANONI, MARCO

    2015-01-01

    Studies of the development of organisms can reveal crucial information on homology of structures. Developmental data are not peculiar to living organisms, and they are routinely preserved in the mineralized tissues that comprise the vertebrate skeleton, allowing us to obtain direct insight into the developmental evolution of this most formative of vertebrate innovations. The pattern of developmental processes is recorded in fossils as successive stages inferred from the gross morphology of multiple specimens and, more reliably and routinely, through the ontogenetic stages of development seen in the skeletal histology of individuals. Traditional techniques are destructive and restricted to a 2-D plane with the third dimension inferred. Effective non-invasive methods of visualizing paleohistology to reconstruct developmental stages of the skeleton are necessary. In a brief survey of paleohistological techniques we discuss the pros and cons of these methods. The use of tomographic methods to reconstruct development of organs is exemplified by the study of the placoderm dentition. Testing evidence for the presence of teeth in placoderms, the first jawed vertebrates, we compare the methods that have been used. These include inferring the development from morphology, and using serial sectioning, microCT or synchrotron X-ray tomographic microscopy (SRXTM) to reconstruct growth stages and directions of growth. The ensuing developmental interpretations are biased by the methods and degree of inference. The most direct and reliable method is using SRXTM data to trace sclerochronology. The resulting developmental data can be used to resolve homology and test hypotheses on the origin of evolutionary novelties. PMID:26306050

  10. Vertebral Body Growth After Craniospinal Irradiation

    SciTech Connect

    Hartley, Katherine A.; Li Chenghong; Laningham, Fred H.; Krasin, Matthew J.; Xiong Xiaoping; Merchant, Thomas E.

    2008-04-01

    Purpose: To estimate the effects of radiotherapy and clinical factors on vertebral growth in patients with medulloblastoma and supratentorial primitive neuroectodermal tumors treated with craniospinal irradiation (CSI) and chemotherapy. Methods and Materials: The height of eight individual or grouped vertebral bodies (C3, C3-C4, T4, T4-T5, C6-T3, T4-T7, L3, L1-L5) was measured before and after CSI (23.4 or 36-39.6 Gy) in 61 patients. Of the 61 patients, 40 were boys and 21 were girls (median age, 7 years; range, 3-13 years), treated between October 1996 and October 2003. Sagittal T{sub 1}-weighted magnetic resonance images were used for the craniocaudal measurements. The measurements numbered 275 (median, 5/patient; range, 3-7). The median follow-up after CSI was 44.1 months (range, 13.8-74.9 months). Results: Significant growth was observed in all measured vertebrae. Excluding C3-C4, the growth rate of the grouped vertebrae was affected by age, gender, and CSI dose (risk classification). The risk classification alone affected the growth rates of C3 (p = 0.002) and L3 (p = 0.02). Before CSI, the length of all vertebral bodies was an increasing function of age (p <0.0001). The C3 length before CSI was affected by gender and risk classification: C3 was longer for female (p = 0.07) and high-risk (p = 0.07) patients. Conclusion: All vertebrae grew significantly after CSI, with the vertebrae of the boys and younger patients growing at a rate greater than that of their counterparts. The effect of age was similar across all vertebrae, and gender had the greatest effect on the growth of the lower cervical and upper thoracic vertebrae. The effect of the risk classification was greatest in the lumbar spine by a factor of {<=}10.

  11. A molecular and genetic outline of cardiac morphogenesis.

    PubMed

    Rana, M S; Christoffels, V M; Moorman, A F M

    2013-04-01

    Perturbations in cardiac development result in congenital heart disease, the leading cause of birth defect-related infant morbidity and mortality. Advances in cardiac developmental biology have significantly augmented our understanding of signalling pathways and transcriptional networks underlying heart formation. Cardiogenesis is initiated with the formation of mesodermal multipotent cardiac progenitor cells and is governed by cross-talk between developmental cues emanating from endodermal, mesodermal and ectodermal cells. The molecular and transcriptional machineries that direct the specification and differentiation of these cardiac precursors are part of an evolutionarily conserved programme that includes the Nkx-, Gata-, Hand-, T-box- and Mef2 family of transcription factors. Unravelling the hierarchical networks governing the fate and differentiation of cardiac precursors is crucial for our understanding of congenital heart disease and future stem cell-based and gene therapies. Recent molecular and genetic lineage analyses have revealed that subpopulations of cardiac progenitor cells follow distinctive specification and differentiation paths, which determine their final contribution to the heart. In the last decade, progenitor cells that contribute to the arterial pole and right ventricle have received much attention, as abnormal development of these cells frequently results in congenital defects of the aortic and pulmonary outlets, representing the most commonly occurring congenital cardiac defects. In this review, we provide an overview of the building plan of the vertebrate four-chambered heart, with a special focus on cardiac progenitor cell specification, differentiation and deployment during arterial pole development. PMID:23297764

  12. Evaluation and Management of Vertebral Compression Fractures

    PubMed Central

    Alexandru, Daniela; So, William

    2012-01-01

    Compression fractures affect many individuals worldwide. An estimated 1.5 million vertebral compression fractures occur every year in the US. They are common in elderly populations, and 25% of postmenopausal women are affected by a compression fracture during their lifetime. Although these fractures rarely require hospital admission, they have the potential to cause significant disability and morbidity, often causing incapacitating back pain for many months. This review provides information on the pathogenesis and pathophysiology of compression fractures, as well as clinical manifestations and treatment options. Among the available treatment options, kyphoplasty and percutaneous vertebroplasty are two minimally invasive techniques to alleviate pain and correct the sagittal imbalance of the spine. PMID:23251117

  13. Quaternary vertebrates from Greenland: A review

    NASA Astrophysics Data System (ADS)

    Bennike, Ole

    Remains of fishes, birds and mammals are rarely reported from Quaternary deposits in Greenland. The oldest remains come from Late Pliocene and Early Pleistocene deposits and comprise Atlantic cod, hare, rabbit and ringed seal. Interglacial and interstadial deposits have yielded remains of cod, little auk, collared lemming, ringed seal, reindeer and bowhead whale. Early and Mid-Holocene finds include capelin, polar cod, red fish, sculpin, three-spined stickleback, Lapland longspur, Arctic hare, collared lemming, wolf, walrus, ringed seal, reindeer and bowhead whale. It is considered unlikely that vertebrates could survive in Greenland during the peak of the last glaciation, but many species had probably already immigrated in the Early Holocene.

  14. Intracranial Vertebral Artery Dissections: Evolving Perspectives

    PubMed Central

    Ali, M.S.; Amenta, P.S.; Starke, R.M.; Jabbour, P.M.; Gonzalez, L.F.; Tjoumakaris, S.I.; Flanders, A.E.; Rosenwasser, R.H.; Dumont, A.S.

    2012-01-01

    Summary Intracranial vertebral artery dissection (VAD) represents the underlying etiology in a significant percentage of posterior circulation ischemic strokes and subarachnoid hemorrhages. These lesions are particularly challenging in their diagnosis, management, and in the prediction of long-term outcome. Advances in the understanding of underlying processes leading to dissection, as well as the evolution of modern imaging techniques are discussed. The data pertaining to medical management of intracranial VADs, with emphasis on anticoagulants and antiplatelet agents, is reviewed. Surgical intervention is discussed, including, the selection of operative candidates, open and endovascular procedures, and potential complications. The evolution of endovascular technology and techniques is highlighted. PMID:23217643

  15. Molecular evolution of color vision in vertebrates.

    PubMed

    Yokoyama, Shozo

    2002-10-30

    Visual systems of vertebrates exhibit a striking level of diversity, reflecting their adaptive responses to various color environments. The photosensitive molecules, visual pigments, can be synthesized in vitro and their absorption spectra can be determined. Comparing the amino acid sequences and absorption spectra of various visual pigments, we can identify amino acid changes that have modified the absorption spectra of visual pigments. These hypotheses can then be tested using the in vitro assay. This approach has been a powerful tool in elucidating not only the molecular bases of color vision, but the processes of adaptive evolution at the molecular level.

  16. Vertebral pathology in the afar australopithecines.

    PubMed

    Cook, D C; Buikstra, J E; DeRousseau, C J; Johanson, D C

    1983-01-01

    Ten vertebral elements from the AL-288 partial hominid skeleton and 11 elements from the AL-333 collection are described. The AL-288 column presents a marked kyphosis at the level of thoracic vertebrae 6 through 10, with pronounced new bone formation on the ventral surfaces of these vertebrae. These features, associated with narrowed disc space and minor osteophytosis, resemble Scheuermann disease in the human. Even though this diagnosis is consistent with a basically human, bipedal locomotor repertoire, the presence of Scheuermann disease suggests that lifting, climbing, or acrobatic activities may have been important in early hominids.

  17. MiR-2 family targets awd and fng to regulate wing morphogenesis in Bombyx mori.

    PubMed

    Ling, Lin; Ge, Xie; Li, Zhiqian; Zeng, Baosheng; Xu, Jun; Chen, Xu; Shang, Peng; James, Anthony A; Huang, Yongping; Tan, Anjiang

    2015-01-01

    MicroRNAs (miRNAs) are post-transcriptional regulators that target specific mRNAs for repression and thus play key roles in many biological processes, including insect wing morphogenesis. miR-2 is an invertebrate-specific miRNA family that has been predicted in the fruit fly, Drosophila melanogaster, to be involved in regulating the Notch signaling pathway. We show here that miR-2 plays a critical role in wing morphogenesis in the silkworm, Bombyx mori, a lepidopteran model insect. Transgenic over-expression of a miR-2 cluster using a Gal4/UAS system results in deformed adult wings, supporting the conclusion that miR-2 regulates functions essential for normal wing morphogenesis. Two genes, abnormal wing disc (awd) and fringe (fng), which are positive regulators in Notch signaling, are identified as miR-2 targets and validated by a dual-luciferase reporter assay. The relative abundance of both awd and fng expression products was reduced significantly in transgenic animals, implicating them in the abnormal wing phenotype. Furthermore, somatic mutagenesis analysis of awd and fng using the CRISPR/Cas9 system and knock-out mutants also resulted in deformed wings similar to those observed in the miR-2 overexpression transgenic animals. The critical role of miR-2 in Bombyx wing morphogenesis may provide a potential target in future lepidopteran pest control. PMID:26037405

  18. Small heat shock proteins Hspb7 and Hspb12 regulate early steps of cardiac morphogenesis

    PubMed Central

    Rosenfeld, Gabriel E.; Mercer, Emily J.; Mason, Christopher E.; Evans, Todd

    2013-01-01

    Cardiac morphogenesis is a complex multi-stage process, and the molecular basis for controlling distinct steps remains poorly understood. Because gata4 encodes a key transcriptional regulator of morphogenesis, we profiled transcript changes in cardiomyocytes when Gata4 protein is depleted from developing zebrafish embryos. We discovered that gata4 regulates expression of two small heat shock genes, hspb7 and hspb12, both of which are expressed in the embryonic heart. We show that depletion of Hspb7 or Hspb12 disrupts normal cardiac morphogenesis, at least in part due to defects in ventricular size and shape. We confirmed that gata4 interacts genetically with the hspb7/12 pathway, but surprisingly, we found that hspb7 also has an earlier, gata4-independent function. Depletion perturbs Kupffer’s vesicle (KV) morphology leading to a failure in establishing the left-right axis of asymmetry. Targeted depletion of Hspb7 in the yolk syncytial layer is sufficient to disrupt KV morphology and also causes an even earlier block to heart tube formation and a bifid phenotype. Recently, several genome-wide association studies found that HSPB7 SNPs are highly associated with idiopathic cardiomyopathies and heart failure. Therefore, GATA4 and HSPB7 may act alone or together to regulate morphogenesis with relevance to congenital and acquired human heart disease. PMID:23850773

  19. Zebrafish neural tube morphogenesis requires Scribble-dependent oriented cell divisions.

    PubMed

    Žigman, Mihaela; Trinh, Le A; Fraser, Scott E; Moens, Cecilia B

    2011-01-11

    How control of subcellular events in single cells determines morphogenesis on the scale of the tissue is largely unresolved. The stereotyped cross-midline mitoses of progenitors in the zebrafish neural keel provide a unique experimental paradigm for defining the role and control of single-cell orientation for tissue-level morphogenesis in vivo. We show here that the coordinated orientation of individual progenitor cell division in the neural keel is the cellular determinant required for morphogenesis into a neural tube epithelium with a single straight lumen. We find that Scribble is required for oriented cell division and that its function in this process is independent of canonical apicobasal and planar polarity pathways. We identify a role for Scribble in controlling clustering of α-catenin foci in dividing progenitors. Loss of either Scrib or N-cadherin results in abnormally oriented mitoses, reduced cross-midline cell divisions, and similar neural tube defects. We propose that Scribble-dependent nascent cell-cell adhesion clusters between neuroepithelial progenitors contribute to define orientation of their cell division. Finally, our data demonstrate that while oriented mitoses of individual cells determine neural tube architecture, the tissue can in turn feed back on its constituent cells to define their polarization and cell division orientation to ensure robust tissue morphogenesis.

  20. MiR-2 family targets awd and fng to regulate wing morphogenesis in Bombyx mori

    PubMed Central

    Ling, Lin; Ge, Xie; Li, Zhiqian; Zeng, Baosheng; Xu, Jun; Chen, Xu; Shang, Peng; James, Anthony A; Huang, Yongping; Tan, Anjiang

    2015-01-01

    MicroRNAs (miRNAs) are post-transcriptional regulators that target specific mRNAs for repression and thus play key roles in many biological processes, including insect wing morphogenesis. miR-2 is an invertebrate-specific miRNA family that has been predicted in the fruit fly, Drosophila melanogaster, to be involved in regulating the Notch signaling pathway. We show here that miR-2 plays a critical role in wing morphogenesis in the silkworm, Bombyx mori, a lepidopteran model insect. Transgenic over-expression of a miR-2 cluster using a Gal4/UAS system results in deformed adult wings, supporting the conclusion that miR-2 regulates functions essential for normal wing morphogenesis. Two genes, abnormal wing disc (awd) and fringe (fng), which are positive regulators in Notch signaling, are identified as miR-2 targets and validated by a dual-luciferase reporter assay. The relative abundance of both awd and fng expression products was reduced significantly in transgenic animals, implicating them in the abnormal wing phenotype. Furthermore, somatic mutagenesis analysis of awd and fng using the CRISPR/Cas9 system and knock-out mutants also resulted in deformed wings similar to those observed in the miR-2 overexpression transgenic animals. The critical role of miR-2 in Bombyx wing morphogenesis may provide a potential target in future lepidopteran pest control. PMID:26037405

  1. Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis.

    PubMed

    Castelli, Maddalena; Boca, Manila; Chiaravalli, Marco; Ramalingam, Harini; Rowe, Isaline; Distefano, Gianfranco; Carroll, Thomas; Boletta, Alessandra

    2013-01-01

    Several organs, including the lungs and kidneys, are formed by epithelial tubes whose proper morphogenesis ensures correct function. This is best exemplified by the kidney, where defective establishment or maintenance of tubular diameter results in polycystic kidney disease, a common genetic disorder. Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1, a large receptor of unknown function. Here we demonstrate that PC-1 has an essential role in the establishment of correct tubular diameter during nephron development. Polycystin-1 associates with Par3 favouring the assembly of a pro-polarizing Par3/aPKC complex and it regulates a programme of cell polarity important for oriented cell migration and for a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney results in defective convergent extension and tubular morphogenesis, and in renal cyst formation. Our data define Polycystin-1 as central to cell polarization and to epithelial tube morphogenesis and homeostasis. PMID:24153433

  2. A critical role for NF2 and the Hippo pathway in branching morphogenesis

    PubMed Central

    Reginensi, Antoine; Enderle, Leonie; Gregorieff, Alex; Johnson, Randy L.; Wrana, Jeffrey L.; McNeill, Helen

    2016-01-01

    Branching morphogenesis is a complex biological process common to the development of most epithelial organs. Here we demonstrate that NF2, LATS1/2 and YAP play a critical role in branching morphogenesis in the mouse kidney. Removal of Nf2 or Lats1/2 from the ureteric bud (UB) lineage causes loss of branching morphogenesis that is rescued by loss of one copy of Yap and Taz, and phenocopied by YAP overexpression. Mosaic analysis demonstrates that cells with high YAP expression have reduced contribution to UB tips, similar to Ret−/− cells, and that YAP suppresses RET signalling and tip identity. Conversely, Yap/Taz UB-deletion leads to cyst-like branching and expansion of UB tip markers, suggesting a shift towards tip cell identity. Based on these data we propose that NF2 and the Hippo pathway locally repress YAP/TAZ activity in the UB to promote subsequent splitting of the tip to allow branching morphogenesis. PMID:27480037

  3. Roles of EphB3/Ephrin-B1 Interactions in Feather Morphogenesis

    PubMed Central

    Suksaweang, Sanong; Jiang, Ting-Xin; Roybal, Paul; Chuong, Cheng-Ming; Widelitz, Randall

    2013-01-01

    Background The Eph receptor tyrosine kinases and their ephrin ligands are involved in morphogenesis during organ formation. Methods We studied their role in feather morphogenesis, focusing on ephrin-B1 and its receptor EphB3. Results Early in feather development ephrin-B1 is expressed in the dermal condensation, not inter-bud mesenchyme. Later, in feather buds, it is in both epithelium and mesenchyme. In the feather follicle, it is enriched in the feather filament epithelium and marginal plate that sets the boundary between barb ridges. EphB3 also is expressed in epithelia. In the feather bud, its expression is restricted to the posterior bud. In the follicle, its expression forms a circle at the bud base which may set the boundary between bud and inter-bud domains. Perturbation with ephrin-B1-Fc altered feather primordia segregation and feather bud elongation. Conclusion Analyses reveal ephrin-B1-Fc caused three types of changes: blurred placode boundaries with loose dermal condensations, incomplete follicle invagination with less compact dermal papillae, and aberrant barb ridge patterning in feather filament morphogenesis. Thus, while ephrin-B1 suppression does not inhibit the initial emergence of a new epithelial domain, Eph/ephrin-B1 interaction is required for its proper completion. We propose that interaction between ephrin B1 and its receptor is involved in boundary stabilization during feather morphogenesis. PMID:23319347

  4. Sox9 plays multiple roles in the lung epithelium during branching morphogenesis

    PubMed Central

    Rockich, Briana E.; Hrycaj, Steven M.; Shih, Hung Ping; Nagy, Melinda S.; Ferguson, Michael A. H.; Kopp, Janel L.; Sander, Maike; Wellik, Deneen M.; Spence, Jason R.

    2013-01-01

    Lung branching morphogenesis is a highly orchestrated process that gives rise to the complex network of gas-exchanging units in the adult lung. Intricate regulation of signaling pathways, transcription factors, and epithelial–mesenchymal cross-talk are critical to ensuring branching morphogenesis occurs properly. Here, we describe a role for the transcription factor Sox9 during lung branch-ing morphogenesis. Sox9 is expressed at the distal tips of the branching epithelium in a highly dynamic manner as branching occurs and is down-regulated starting at embryonic day 16.5, concurrent with the onset of terminal differentiation of type 1 and type 2 alveolar cells. Using epithelial-specific genetic loss- and gain-of-function approaches, our results demonstrate that Sox9 controls multiple aspects of lung branching. Fine regulation of Sox9 levels is required to balance proliferation and differentiation of epithelial tip progenitor cells, and loss of Sox9 leads to direct and indirect cellular defects including extracellular matrix defects, cytoskeletal disorganization, and aberrant epithelial movement. Our evidence shows that unlike other endoderm-derived epithelial tissues, such as the intestine, Wnt/β-catenin signaling does not regulate Sox9 expression in the lung. We conclude that Sox9 collectively promotes proper branching morphogenesis by controlling the balance between proliferation and differentiation and regulating the extracellular matrix. PMID:24191021

  5. γCOP Is Required for Apical Protein Secretion and Epithelial Morphogenesis in Drosophila melanogaster

    PubMed Central

    Grieder, Nicole C.; Caussinus, Emmanuel; Parker, David S.; Cadigan, Kenneth; Affolter, Markus; Luschnig, Stefan

    2008-01-01

    Background There is increasing evidence that tissue-specific modifications of basic cellular functions play an important role in development and disease. To identify the functions of COPI coatomer-mediated membrane trafficking in Drosophila development, we were aiming to create loss-of-function mutations in the γCOP gene, which encodes a subunit of the COPI coatomer complex. Principal Findings We found that γCOP is essential for the viability of the Drosophila embryo. In the absence of zygotic γCOP activity, embryos die late in embryogenesis and display pronounced defects in morphogenesis of the embryonic epidermis and of tracheal tubes. The coordinated cell rearrangements and cell shape changes during tracheal tube morphogenesis critically depend on apical secretion of certain proteins. Investigation of tracheal morphogenesis in γCOP loss-of-function mutants revealed that several key proteins required for tracheal morphogenesis are not properly secreted into the apical lumen. As a consequence, γCOP mutants show defects in cell rearrangements during branch elongation, in tube dilation, as well as in tube fusion. We present genetic evidence that a specific subset of the tracheal defects in γCOP mutants is due to the reduced secretion of the Zona Pellucida protein Piopio. Thus, we identified a critical target protein of COPI-dependent secretion in epithelial tube morphogenesis. Conclusions/Significance These studies highlight the role of COPI coatomer-mediated vesicle trafficking in both general and tissue-specific secretion in a multicellular organism. Although COPI coatomer is generally required for protein secretion, we show that the phenotypic effect of γCOP mutations is surprisingly specific. Importantly, we attribute a distinct aspect of the γCOP phenotype to the effect on a specific key target protein. PMID:18802472

  6. Sonic hedgehog cascade is required for penile postnatal morphogenesis, differentiation, and adult homeostasis.

    PubMed

    Podlasek, Carol A; Zelner, David J; Jiang, Hong Bin; Tang, Yi; Houston, John; McKenna, Kevin E; McVary, Kevin T

    2003-02-01

    The penis is unique in that it undergoes morphogenesis and differentiation primarily in the postnatal period. For complex structures such as the penis to be made from undifferentiated precursor cells, proliferation, differentiation, and patterning are required. This process involves coordinated activity of multiple signals. Sonic hedgehog (Shh) forms part of a regulatory cascade that is essential for growth and morphogenesis of many tissues. It is hypothesized that the penis utilizes regulatory mechanisms similar to those of the limb and accessory sex organs to pattern penile postnatal morphogenesis and differentiation and that the Shh cascade is critical to this process. To test this hypothesis, Shh, BMP-4, Ptc, and Hoxa-10 localization and function were examined in Sprague-Dawley rat penes by means of quantitative reverse transcription polymerase chain reaction, in situ hybridization, immunohistochemistry, and Western blotting. These genes were expressed in the penis during postnatal morphogenesis in a spatially and temporally restricted manner in adjacent layers of the corpora cavernosal sinusoids. The function of Shh and BMP-4 is to establish and maintain corpora cavernosal sinusoids. The data suggest that Ptc and Hoxa-10 are also important in penile morphogenesis. The continuing function of Shh and targets of its signaling in maintaining penile homeostasis in the adult is significant because disruption of Shh signaling affects erectile function. This is the first report that demonstrates the significant role that Shh plays in establishing and maintaining penile homeostasis and how this relates to erectile function. These studies provide valuable insight that may be applied to improve treatment options for erectile dysfunction. PMID:12533405

  7. Adenosine Kinase Modulates Root Gravitropism and Cap Morphogenesis in Arabidopsis1[W][OA

    PubMed Central

    Young, Li-Sen; Harrison, Benjamin R.; U.M., Narayana Murthy; Moffatt, Barbara A.; Gilroy, Simon; Masson, Patrick H.

    2006-01-01

    Adenosine kinase (ADK) is a key enzyme that regulates intra- and extracellular levels of adenosine, thereby modulating methyltransferase reactions, production of polyamines and secondary compounds, and cell signaling in animals. Unfortunately, little is known about ADK's contribution to the regulation of plant growth and development. Here, we show that ADK is a modulator of root cap morphogenesis and gravitropism. Upon gravistimulation, soluble ADK levels and activity increase in the root tip. Mutation in one of two Arabidopsis (Arabidopsis thaliana) ADK genes, ADK1, results in cap morphogenesis defects, along with alterations in root sensitivity to gravistimulation and slower kinetics of root gravitropic curvature. The kinetics defect can be partially rescued by adding spermine to the growth medium, whereas the defects in cap morphogenesis and gravitropic sensitivity cannot. The root morphogenesis and gravitropism defects of adk1-1 are accompanied by altered expression of the PIN3 auxin efflux facilitator in the cap and decreased expression of the auxin-responsive DR5-GUS reporter. Furthermore, PIN3 fails to relocalize to the bottom membrane of statocytes upon gravistimulation. Consequently, adk1-1 roots cannot develop a lateral auxin gradient across the cap, necessary for the curvature response. Interestingly, adk1-1 does not affect gravity-induced cytoplasmic alkalinization of the root statocytes, suggesting either that ADK1 functions between cytoplasmic alkalinization and PIN3 relocalization in a linear pathway or that the pH and PIN3-relocalization responses to gravistimulation belong to distinct branches of the pathway. Our data are consistent with a role for ADK and the S-adenosyl-l-methionine pathway in the control of root gravitropism and cap morphogenesis. PMID:16891550

  8. Reactive oxygen species in the presence of high glucose alter ureteric bud morphogenesis.

    PubMed

    Zhang, Shao-Ling; Chen, Yun-Wen; Tran, Stella; Chenier, Isabelle; Hébert, Marie-Josée; Ingelfinger, Julie R

    2007-07-01

    Renal malformations are a major cause of childhood renal failure. During the development of the kidney, ureteric bud (UB) branching morphogenesis is critical for normal nephrogenesis. These studies investigated whether renal UB branching morphogenesis is altered by a high ambient glucose environment and studied underlying mechanism(s). Kidney explants that were isolated from different periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence protein mice were cultured for 24 h in either normal d-glucose (5 mM) or high d-glucose (25 mM) medium with or without various inhibitors. Alterations in renal morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2) gene expression was determined by real-time quantitative PCR, Western blotting, and immunohistology. The results revealed that high d-glucose (25 mM) specifically stimulates UB branching morphogenesis via Pax-2 gene expression, whereas other glucose analogs, such as d-mannitol, l-glucose, and 2-deoxy-d-glucose, had no effect. The stimulatory effect of high glucose on UB branching was blocked in the presence of catalase and inhibitors of NADPH oxidase, mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized in UB), acceleration of UB branching but not nephron formation. Taken together, these data demonstrate that high glucose alters UB branching morphogenesis. This occurs, at least in part, via reactive oxygen species generation, activation of Akt signaling, and upregulation of Pax-2 gene expression.

  9. Identifying Synonymous Regulatory Elements in Vertebrate Genomes

    SciTech Connect

    Ovcharenko, I; Nobrega, M A

    2005-02-07

    Synonymous gene regulation, defined as driving shared temporal and/or spatial expression of groups of genes, is likely predicated on genomic elements that contain similar modules of certain transcription factor binding sites (TFBS). We have developed a method to scan vertebrate genomes for evolutionary conserved modules of TFBS in a predefined configuration, and created a tool, named SynoR that identify synonymous regulatory elements (SREs) in vertebrate genomes. SynoR performs de novo identification of SREs utilizing known patterns of TFBS in active regulatory elements (REs) as seeds for genome scans. Layers of multiple-species conservation allow the use of differential phylogenetic sequence conservation filters in the search of SREs and the results are displayed as to provide an extensive annotation of genes containing detected REs. Gene Ontology categories are utilized to further functionally classify the identified genes, and integrated GNF Expression Atlas 2 data allow the cataloging of tissue-specificities of the predicted SREs. We illustrate how this new tool can be used to establish a linkage between human diseases and noncoding genomic content. SynoR is publicly available at http://synor.dcode.org.

  10. HOVERGEN: a database of homologous vertebrate genes.

    PubMed Central

    Duret, L; Mouchiroud, D; Gouy, M

    1994-01-01

    Comparison of homologous genes is a major step for many studies related to genome structure, function or evolution. Similarity search programs easily find genes homologous to a given sequence. However, only very tedious manual procedures allow the retrieval of all sets of homologous genes sequenced for a given set of species. Moreover, this search often generates errors due to the complexity of data to be managed simultaneously: phylogenetic trees, alignments, taxonomy, sequences and related information. HOVERGEN helps to solve these problems by integrating all this information. HOVERGEN corresponds to GenBank sequences from all vertebrate species, with some data corrected, clarified, or completed, notably to address the problem of redundancy. Coding sequences have been classified in gene families. Protein multiple alignments and phylogenetic trees have been calculated for each family. Sequences and related information have been structured in an ACNUC database which permits complex selections. A graphical interface has been developed to visualize and edit trees. Genes are displayed in color, according to their taxonomy. Users have directly access to all information attached to sequences and to multiple alignments simply by clicking on genes. This graphical tool gives thus a rapid and simple access to all data necessary to interpret homology relationships between genes. HOVERGEN allows the user to easily select sets of homologous vertebrate genes, and thus is particularly useful for comparative sequence analysis, or molecular evolution studies. Images PMID:8036164

  11. What can vertebrates tell us about segmentation?

    PubMed Central

    2014-01-01

    Segmentation is a feature of the body plans of a number of diverse animal groupings, including the annelids, arthropods and chordates. However, it has been unclear whether or not these different manifestations of segmentation are independently derived or have a common origin. Central to this issue is whether or not there are common developmental mechanisms that establish segmentation and the evolutionary origins of these processes. A fruitful way to address this issue is to consider how segmentation in vertebrates is directed. During vertebrate development three different segmental systems are established: the somites, the rhombomeres and the pharyngeal arches. In each an iteration of parts along the long axis is established. However, it is clear that the formation of the somites, rhombomeres or pharyngeal arches have little in common, and as such there is no single segmentation process. These different segmental systems also have distinct evolutionary histories, thus highlighting the fact that segmentation can and does evolve independently at multiple points. We conclude that the term segmentation indicates nothing more than a morphological description and that it implies no mechanistic similarity. Thus it is probable that segmentation has arisen repeatedly during animal evolution. PMID:25009737

  12. Generation of Viable Plant-Vertebrate Chimeras.

    PubMed

    Alvarez, Marjorie; Reynaert, Nicole; Chávez, Myra N; Aedo, Geraldine; Araya, Francisco; Hopfner, Ursula; Fernández, Juan; Allende, Miguel L; Egaña, José T

    2015-01-01

    The extreme dependence on external oxygen supply observed in animals causes major clinical problems and several diseases are related to low oxygen tension in tissues. The vast majority of the animals do not produce oxygen but a few exceptions have shown that photosynthetic capacity is physiologically compatible with animal life. Such symbiotic photosynthetic relationships are restricted to a few aquatic invertebrates. In this work we aimed to explore if we could create a chimerical organism by incorporating photosynthetic eukaryotic cells into a vertebrate animal model. Here, the microalgae Chlamydomonas reinhardtii was injected into zebrafish eggs and the interaction and viability of both organisms were studied. Results show that microalgae were distributed into different tissues, forming a fish-alga chimera organism for a prolonged period of time. In addition, microscopic observation of injected algae, in vivo expression of their mRNA and re-growth of the algae ex vivo suggests that they survived to the developmental process, living for several days after injection. Moreover microalgae did not trigger a significant inflammatory response in the fish. This work provides additional evidence to support the possibility that photosynthetic vertebrates can be engineered. PMID:26126202

  13. Flexible device for vertebral body replacement.

    PubMed

    Main, J A; Wells, M E; Spengler, D M; Strauss, A M; Keller, T S

    1989-03-01

    A novel vertebral prosthesis is presented. The prosthesis was developed for surgical procedures requiring the resection of a complete vertebral body and the adjacent intervertebral discs, the design objective being to develop a flexible implant that would be robust enough to withstand the in vivo stress environment of the human spine. In theory, a flexible implant should preserve a more normal range of motion and apply less stress to surrounding tissue than a rigid implant. A prototype implant was constructed so as to combine a rigid stainless steel structure with flexible silicon rubber elements in order to form an implant with static and dynamic mechanical characteristics similar to those of the anterior spinal column. Implant flexibility characteristics were determined from ex vivo stress-strain behaviour during bending and compressive creep testing. Results from the bending tests indicated good agreement for the lateral and sagittal bending characteristics in comparison with in vitro bending tests of human lumbar motion segments. Comparison of the implant compressive creep response with similar in vitro tests on human lumbar intervertebral discs also demonstrated similarities in the time-dependent mechanical parameters. PMID:2704210

  14. Sensing and surviving hypoxia in vertebrates.

    PubMed

    Jonz, Michael G; Buck, Leslie T; Perry, Steve F; Schwerte, Thorsten; Zaccone, Giacomo

    2016-02-01

    Surviving hypoxia is one of the most critical challenges faced by vertebrates. Most species have adapted to changing levels of oxygen in their environment with specialized organs that sense hypoxia, while only few have been uniquely adapted to survive prolonged periods of anoxia. The goal of this review is to present the most recent research on oxygen sensing, adaptation to hypoxia, and mechanisms of anoxia tolerance in nonmammalian vertebrates. We discuss the respiratory structures in fish, including the skin, gills, and air-breathing organs, and recent evidence for chemosensory neuroepithelial cells (NECs) in these tissues that initiate reflex responses to hypoxia. The use of the zebrafish as a genetic and developmental model has allowed observation of the ontogenesis of respiratory and chemosensory systems, demonstration of a putative intracellular O2 sensor in chemoreceptors that may initiate transduction of the hypoxia signal, and investigation into the effects of extreme hypoxia on cardiorespiratory development. Other organisms, such as goldfish and freshwater turtles, display a high degree of anoxia tolerance, and these models are revealing important adaptations at the cellular level, such as the regulation of glutamatergic and GABAergic neurotransmission in defense of homeostasis in central neurons.

  15. "Ostrich sign" indicates bilateral vertebral artery dissection.

    PubMed

    Rose, David Z; Husain, M Rizwan

    2012-11-01

    Vertebral artery dissections (VADs) comprise about 2% of ischemic strokes and can be associated with trauma, chiropractic manipulation, motor vehicle collisions, whiplash, amusement park rides, golfing, and other motion-induced injuries to the neck. We present a case of bilateral extracranial VAD as a complication of conducting an orchestra. To our knowledge, this has not been documented in the literature. Conceivably, vigorous neck twisting in an inexperienced, amateur conductor may place excessive rotational forces upon mobile portions of the verterbral arteries, tear the intima, deposit subintimal blood that extends longitudinally, and cause neck pain and/or posterior fossa ischemic symptoms. Magnetic resonance angiography examinations of axially oriented slices of bilateral VADs resemble the face of an ostrich. This observation is similar to the "puppy sign," in which bilateral internal carotid artery dissections resemble the face of a dog. Craniocervical dissections of either the carotid or vertebral arteries have the potential to form an aneurysm, cause artery-to-artery embolism, or completely occlude the parent artery, resulting in an ischemic stroke. Because bilateral VADs in axial magnetic resonance angiographic sections stand out like the eyes of an ostrich, and because the fast identification of VADs is so critical, we eponymize this image the "ostrich sign."

  16. Generation of Viable Plant-Vertebrate Chimeras

    PubMed Central

    Aedo, Geraldine; Araya, Francisco; Hopfner, Ursula; Fernández, Juan; Allende, Miguel L.; Egaña, José T.

    2015-01-01

    The extreme dependence on external oxygen supply observed in animals causes major clinical problems and several diseases are related to low oxygen tension in tissues. The vast majority of the animals do not produce oxygen but a few exceptions have shown that photosynthetic capacity is physiologically compatible with animal life. Such symbiotic photosynthetic relationships are restricted to a few aquatic invertebrates. In this work we aimed to explore if we could create a chimerical organism by incorporating photosynthetic eukaryotic cells into a vertebrate animal model. Here, the microalgae Chlamydomonas reinhardtii was injected into zebrafish eggs and the interaction and viability of both organisms were studied. Results show that microalgae were distributed into different tissues, forming a fish-alga chimera organism for a prolonged period of time. In addition, microscopic observation of injected algae, in vivo expression of their mRNA and re-growth of the algae ex vivo suggests that they survived to the developmental process, living for several days after injection. Moreover microalgae did not trigger a significant inflammatory response in the fish. This work provides additional evidence to support the possibility that photosynthetic vertebrates can be engineered. PMID:26126202

  17. The characters of Palaeozoic jawed vertebrates

    PubMed Central

    Brazeau, Martin D; Friedman, Matt

    2014-01-01

    Newly discovered fossils from the Silurian and Devonian periods are beginning to challenge embedded perceptions about the origin and early diversification of jawed vertebrates (gnathostomes). Nevertheless, an explicit cladistic framework for the relationships of these fossils relative to the principal crown lineages of the jawed vertebrates (osteichthyans: bony fishes and tetrapods; chondrichthyans: sharks, batoids, and chimaeras) remains elusive. We critically review the systematics and character distributions of early gnathostomes and provide a clearly stated hierarchy of synapomorphies covering the jaw-bearing stem gnathostomes and osteichthyan and chondrichthyan stem groups. We show that character lists, designed to support the monophyly of putative groups, tend to overstate their strength and lack cladistic corroboration. By contrast, synapomorphic hierarchies are more open to refutation and must explicitly confront conflicting evidence. Our proposed synapomorphy scheme is used to evaluate the status of the problematic fossil groups Acanthodii and Placodermi, and suggest profitable avenues for future research. We interpret placoderms as a paraphyletic array of stem-group gnathostomes, and suggest what we regard as two equally plausible placements of acanthodians: exclusively on the chondrichthyan stem, or distributed on both the chondrichthyan and osteichthyan stems. PMID:25750460

  18. Permo-Triassic vertebrate extinctions: A program

    NASA Technical Reports Server (NTRS)

    Olson, E. C.

    1988-01-01

    Since the time of the Authors' study on this subject, a great deal of new information has become available. Concepts of the nature of extinctions have changed materially. The Authors' conclusion that a catastrophic event was not responsible for the extinction of vertebrates has modified to the extent that hypotheses involving either the impact of a massive extra-terrestrial body or volcanism provide plausible but not currently fully testable hypotheses. Stated changes resulted in a rapid decrease in organic diversity, as the ratio of origins of taxa to extinctions shifted from strongly positive to negative, with momentary equilibrium being reached at about the Permo-Triassic boundary. The proximate causes of the changes in the terrestrial biota appear to lie in two primary factors: (1) strong climatic changes (global mean temperatures, temperature ranges, humidity) and (2) susceptibility of the dominant vertebrates (large dicynodonts) and the glossopteris flora to disruption of the equlibrium of the world ecosystem. The following proximate causes have been proposed: (1) rhythmic fluctuations in solar radiation, (2) tectonic events as Pangea assembled, altering land-ocean relationships, patterns of wind and water circulation and continental physiography, (3) volcanism, and (4) changes subsequent to impacts of one or more massive extra terrestrial objects, bodies or comets. These hypotheses are discussed.

  19. The evolution of vertebrate opioid receptors

    PubMed Central

    Stevens, Craig W.

    2011-01-01

    The proteins that mediate the analgesic and other effects of opioid drugs and endogenous opioid peptides are known as opioid receptors. Opioid receptors consist of a family of four closely-related proteins belonging to the large superfamily of G-protein coupled receptors. The three types of opioid receptors shown unequivocally to mediate analgesia in animal models are the mu (MOR), delta (DOR), and kappa (KOR) opioid receptor proteins. The role of the fourth member of the opioid receptor family, the nociceptin or orphanin FQ receptor (ORL), is not as clear as hyperalgesia, analgesia, and no effect was reported after administration of ORL agonists. There are now cDNA sequences for all four types of opioid receptors that are expressed in the brain of six species from three different classes of vertebrates. This review presents a comparative analysis of vertebrate opioid receptors using bioinformatics and data from recent human genome studies. Results indicate that opioid receptors arose by gene duplication, that there is a vector of opioid receptor divergence, and that MOR shows evidence of rapid evolution. PMID:19273128

  20. Aberrant Origin of Vertebral Artery and its Clinical Implications

    PubMed Central

    Yuan, Shi-Min

    2016-01-01

    Aberrant origin of vertebral artery is rare. The anatomical features and clinical significance of this lesion remain to be clarified. A comprehensive collection of the pertinent literature resulted in a cohort of 1286 cases involving 955 patients and 331 cadavers. There were more left than right and more unilateral than bilateral aberrant vertebral arteries. Patients with aberrant origin of vertebral artery were often asymptomatic and in only 5.5% of the patients their symptoms were probably related to the aberrant origin of vertebral artery. The acquired cardiovascular lesions were present in 9.5% of the patients, 20.9% of which were vertebral artery-associated lesions. Eight (0.8%) patients had a vertebral artery dissection. Logistic regression analysis showed significant regressions between bovine trunk and left vertebral artery (P=0.000), between the dual origins of vertebral artery and cerebral infarct/thrombus (P=0.041), between associated alternative congenital vascular variants and cervical/aortic dissection/atherosclerosis (P=0.008). Multiple logistic regression demonstrated that side of the aberrant origin of vertebral artery (left vertebral artery) (P=0.014), arch branch pattern (direct arch origin) (P=0.019), presence of the common trunk (P=0.019), associated acquired vascular disorder (P=0.034) and the patients who warranted management (P=0.000) were significant risk predictors for neurological sequelea. The patients with neurological symptoms and those for neck and chest operations/ interventions should be carefully screened for the possibility of an aberrant origin of vertebral artery. The results from the cadaver metrology study are very helpful in the design of the aortic stent. The arch branch pattern has to be taken into consideration before any maneuver in the local region so as to avoid unexpected events in relation to aberrant vertebral artery. PMID:27074275