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Sample records for morphogenesis vertebral mineralization

  1. 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. PMID:27025884

  2. 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

  3. 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

  4. GONAD MORPHOGENESIS IN VERTEBRATES: DIVERGENT MEANS TO A CONVERGENT END

    PubMed Central

    DeFalco, Tony; Capel, Blanche

    2015-01-01

    A critical element of successful sexual reproduction is the generation of sexually dimorphic adult reproductive organs, the testis and ovary, which produce functional gametes. The examination of different vertebrate species shows that the adult gonad is remarkably similar in its morphology across different phylogenetic classes. Surprisingly, however, the cellular and molecular programs employed to create similar organs are not evolutionarily conserved. We highlight the mechanisms used by different vertebrate model systems to generate the somatic architecture necessary to support gametogenesis. In addition, we examine the different vertebrate patterns of germ cell migration from their site of origin to colonize the gonad, and highlight their roles in sex-specific morphogenesis. We also discuss the plasticity of the adult gonad and consider how different genetic and environmental conditions can induce transitions between testis and ovary morphology. PMID:19807280

  5. Control of Vertebrate Skeletal Mineralization by Polyphosphates

    PubMed Central

    Omelon, Sidney; Georgiou, John; Henneman, Zachary J.; Wise, Lisa M.; Sukhu, Balram; Hunt, Tanya; Wynnyckyj, Chrystia; Holmyard, Douglas; Bielecki, Ryszard; Grynpas, Marc D.

    2009-01-01

    Background Skeletons are formed in a wide variety of shapes, sizes, and compositions of organic and mineral components. Many invertebrate skeletons are constructed from carbonate or silicate minerals, whereas vertebrate skeletons are instead composed of a calcium phosphate mineral known as apatite. No one yet knows why the dynamic vertebrate skeleton, which is continually rebuilt, repaired, and resorbed during growth and normal remodeling, is composed of apatite. Nor is the control of bone and calcifying cartilage mineralization well understood, though it is thought to be associated with phosphate-cleaving proteins. Researchers have assumed that skeletal mineralization is also associated with non-crystalline, calcium- and phosphate-containing electron-dense granules that have been detected in vertebrate skeletal tissue prepared under non-aqueous conditions. Again, however, the role of these granules remains poorly understood. Here, we review bone and growth plate mineralization before showing that polymers of phosphate ions (polyphosphates: (PO3−)n) are co-located with mineralizing cartilage and resorbing bone. We propose that the electron-dense granules contain polyphosphates, and explain how these polyphosphates may play an important role in apatite biomineralization. Principal Findings/Methodology The enzymatic formation (condensation) and destruction (hydrolytic degradation) of polyphosphates offers a simple mechanism for enzymatic control of phosphate accumulation and the relative saturation of apatite. Under circumstances in which apatite mineral formation is undesirable, such as within cartilage tissue or during bone resorption, the production of polyphosphates reduces the free orthophosphate (PO43−) concentration while permitting the accumulation of a high total PO43− concentration. Sequestering calcium into amorphous calcium polyphosphate complexes can reduce the concentration of free calcium. The resulting reduction of both free PO43− and free

  6. Meis homeoproteins directly regulate Pax6 during vertebrate lens morphogenesis

    PubMed Central

    Zhang, Xin; Friedman, Adam; Heaney, Shaun; Purcell, Patricia; Maas, Richard L.

    2002-01-01

    Pax6 is a pivotal regulator of eye development throughout Metazoa, but the direct upstream regulators of vertebrate Pax6 expression are unknown. In vertebrates, Pax6 is required for formation of the lens placode, an ectodermal thickening that precedes lens development. Here we show that the Meis1 and Meis2 homeoproteins are direct regulators of Pax6 expression in prospective lens ectoderm. In mice, Meis1 and Meis2 are developmentally expressed in a pattern remarkably similar to Pax6 and their expression is Pax6-independent. Biochemical and transgenic experiments reveal that Meis1 and Meis2 bind a specific sequence in the Pax6 lens placode enhancer that is required for its activity. Furthermore, Pax6 and Meis2 exhibit a strong genetic interaction in lens development, and Pax6 expression is elevated in lenses of Meis2-overexpressing transgenic mice. When expressed in embryonic lens ectoderm, dominant-negative forms of Meis down-regulate endogenous Pax6. These results contrast with those in Drosophila, where the single Meis homolog, Homothorax, has been shown to negatively regulate eye formation. Therefore, despite the striking evolutionary conservation of Pax6 function, Pax6 expression in the vertebrate lens is uniquely regulated. PMID:12183364

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

    PubMed

    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. PMID:18668221

  8. 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.

  9. Dynamic coupling of pattern formation and morphogenesis in the developing vertebrate retina.

    PubMed

    Picker, Alexander; Cavodeassi, Florencia; Machate, Anja; Bernauer, Sabine; Hans, Stefan; Abe, Gembu; Kawakami, Koichi; Wilson, Stephen W; Brand, Michael

    2009-10-01

    During embryonic development, pattern formation must be tightly synchronized with tissue morphogenesis to coordinate the establishment of the spatial identities of cells with their movements. In the vertebrate retina, patterning along the dorsal-ventral and nasal-temporal (anterior-posterior) axes is required for correct spatial representation in the retinotectal map. However, it is unknown how specification of axial cell positions in the retina occurs during the complex process of early eye morphogenesis. Studying zebrafish embryos, we show that morphogenetic tissue rearrangements during eye evagination result in progenitor cells in the nasal half of the retina primordium being brought into proximity to the sources of three fibroblast growth factors, Fgf8/3/24, outside the eye. Triple-mutant analysis shows that this combined Fgf signal fully controls nasal retina identity by regulating the nasal transcription factor Foxg1. Surprisingly, nasal-temporal axis specification occurs very early along the dorsal-ventral axis of the evaginating eye. By in vivo imaging GFP-tagged retinal progenitor cells, we find that subsequent eye morphogenesis requires gradual tissue compaction in the nasal half and directed cell movements into the temporal half of the retina. Balancing these processes drives the progressive alignment of the nasal-temporal retina axis with the anterior-posterior body axis and is controlled by a feed-forward effect of Fgf signaling on Foxg1-mediated cell cohesion. Thus, the mechanistic coupling and dynamic synchronization of tissue patterning with morphogenetic cell behavior through Fgf signaling leads to the graded allocation of cell positional identity in the eye, underlying retinotectal map formation. PMID:19823566

  10. Dynamic Coupling of Pattern Formation and Morphogenesis in the Developing Vertebrate Retina

    PubMed Central

    Picker, Alexander; Cavodeassi, Florencia; Machate, Anja; Bernauer, Sabine; Hans, Stefan; Abe, Gembu; Kawakami, Koichi; Wilson, Stephen W.; Brand, Michael

    2009-01-01

    During embryonic development, pattern formation must be tightly synchronized with tissue morphogenesis to coordinate the establishment of the spatial identities of cells with their movements. In the vertebrate retina, patterning along the dorsal-ventral and nasal-temporal (anterior-posterior) axes is required for correct spatial representation in the retinotectal map. However, it is unknown how specification of axial cell positions in the retina occurs during the complex process of early eye morphogenesis. Studying zebrafish embryos, we show that morphogenetic tissue rearrangements during eye evagination result in progenitor cells in the nasal half of the retina primordium being brought into proximity to the sources of three fibroblast growth factors, Fgf8/3/24, outside the eye. Triple-mutant analysis shows that this combined Fgf signal fully controls nasal retina identity by regulating the nasal transcription factor Foxg1. Surprisingly, nasal-temporal axis specification occurs very early along the dorsal-ventral axis of the evaginating eye. By in vivo imaging GFP-tagged retinal progenitor cells, we find that subsequent eye morphogenesis requires gradual tissue compaction in the nasal half and directed cell movements into the temporal half of the retina. Balancing these processes drives the progressive alignment of the nasal-temporal retina axis with the anterior-posterior body axis and is controlled by a feed-forward effect of Fgf signaling on Foxg1-mediated cell cohesion. Thus, the mechanistic coupling and dynamic synchronization of tissue patterning with morphogenetic cell behavior through Fgf signaling leads to the graded allocation of cell positional identity in the eye, underlying retinotectal map formation. PMID:19823566

  11. Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution.

    PubMed

    Chuong, C M; Patel, N; Lin, J; Jung, H S; Widelitz, R B

    2000-11-01

    Vertebrate epithelial appendages are elaborate topological transformations of flat epithelia into complex organs that either protrude out of external (integument) and internal (oral cavity, gut) epithelia, or invaginate into the surrounding mesenchyme. Although they have specific structures and diverse functions, most epithelial appendages share similar developmental stages, including induction, morphogenesis, differentiation and cycling. The roles of the SHH pathway are analyzed in exemplary organs including feather, hair, tooth, tongue papilla, lung and foregut. SHH is not essential for induction and differentiation, but is involved heavily in morphogenetic processes including cell proliferation (size regulation), branching morphogenesis, mesenchymal condensation, fate determination (segmentation), polarizing activities and so on. Through differential activation of these processes by SHH in a spatiotemporal-specific fashion, organs of different shape and size are laid down. During evolution, new links of developmental pathways may occur and novel forms of epithelial appendages may emerge, upon which evolutionary selections can act. Sites of major variations have progressed from the body plan to the limb plan to the epithelial appendage plan. With its powerful morphogenetic activities, the SHH pathway would likely continue to play a major role in the evolution of novel epithelial appendages. PMID:11130174

  12. The origin of conodonts and of vertebrate mineralized skeletons

    USGS Publications Warehouse

    Murdock, Duncan J.E.; Dong, Xi-Ping; Repetski, John E.; Marone, Federica; Stampanoni, Marco; Donoghue, Philip C.J.

    2013-01-01

    Conodonts are an extinct group of jawless vertebrates whose tooth-like elements are the earliest instance of a mineralized skeleton in the vertebrate lineage, inspiring the ‘inside-out’ hypothesis that teeth evolved independently of the vertebrate dermal skeleton and before the origin of jaws. However, these propositions have been based on evidence from derived euconodonts. Here we test hypotheses of a paraconodont ancestry of euconodonts using synchrotron radiation X-ray tomographic microscopy to characterize and compare the microstructure of morphologically similar euconodont and paraconodont elements. Paraconodonts exhibit a range of grades of structural differentiation, including tissues and a pattern of growth common to euconodont basal bodies. The different grades of structural differentiation exhibited by paraconodonts demonstrate the stepwise acquisition of euconodont characters, resolving debate over the relationship between these two groups. By implication, the putative homology of euconodont crown tissue and vertebrate enamel must be rejected as these tissues have evolved independently and convergently. Thus, the precise ontogenetic, structural and topological similarities between conodont elements and vertebrate odontodes appear to be a remarkable instance of convergence. The last common ancestor of conodonts and jawed vertebrates probably lacked mineralized skeletal tissues. The hypothesis that teeth evolved before jaws and the inside-out hypothesis of dental evolution must be rejected; teeth seem to have evolved through the extension of odontogenic competence from the external dermis to internal epithelium soon after the origin of jaws.

  13. Membranes, minerals, and proteins of developing vertebrate enamel.

    PubMed

    Diekwisch, Thomas G H; Berman, Brett J; Anderton, Xochitl; Gurinsky, Brian; Ortega, Adam J; Satchell, Paul G; Williams, Mia; Arumugham, Chithra; Luan, Xianghong; McIntosh, James E; Yamane, Akira; Carlson, David S; Sire, Jean-Yves; Shuler, Charles F

    2002-12-01

    Developing tooth enamel is formed as organized mineral in a specialized protein matrix. In order to analyze patterns of enamel mineralization and enamel protein expression in species representative of the main extant vertebrate lineages, we investigated developing teeth in a chondrichthyan, the horn shark, a teleost, the guppy, a urodele amphibian, the Mexican axolotl, an anuran amphibian, the leopard frog, two lepidosauria, a gecko and an iguana, and two mammals, a marsupial, the South American short-tailed gray opossum, and the house mouse. Electron microscopic analysis documented the presence of a distinct basal lamina in all species investigated. Subsequent stages of enamel biomineralization featured highly organized long and parallel enamel crystals in mammals, lepidosaurians, the frog, and the shark, while amorphous mineral deposits and/or randomly oriented crystals were observed in the guppy and the axolotl. In situ hybridization using a full-length mouse probe for amelogenin mRNA resulted in amelogenin specific signals in mouse, opossum, gecko, frog, axolotl, and shark. Using immunohistochemistry, amelogenin and tuftelin enamel proteins were detected in the enamel organ of many species investigated, but tuftelin epitopes were also found in other tissues. The anti-M179 antibody, however, did not react with the guppy and axolotl enameloid matrix. We conclude that basic features of vertebrate enamel/enameloid formation such as the presence of enamel proteins or the mineral deposition along the dentin-enamel junction were highly conserved in vertebrates. There were also differences in terms of enamel protein distribution and mineral organization between the vertebrates lineages. Our findings indicated a correlation between the presence of amelogenins and the presence of long and parallel hydroxyapatite crystals in tetrapods and shark. PMID:12430167

  14. Skeletal morphogenesis of the vertebral column of the miniature hylid frog Acris crepitans, with comments on anomalies.

    PubMed

    Pugener, L Analía; Maglia, Anne M

    2009-01-01

    Although the vertebral columns of anurans have received much study in the last 150 years, few detailed descriptions exist of the skeletal morphogenesis of this anatomical unit. Herein, the ontogeny of the vertebral skeleton of the hylid frog Acris crepitans is described based on cleared and double-stained specimens, radiographs, and 3D reconstructions generated from synchrotron microCT scans. The adult axial formula is 1-7-1-1, and the vertebral centra are epichordal and procoelous. The neural arches are nonimbricate, and there is a medial articulation between the laminae of Presacrals I and II. Free ribs are absent. The sacral diapophyses are uniform in width or slightly expanded distally. The urostyle is slender, round in cross section, and about equal in length to the presacral region. Presacral vertebrae are the first to form, developing in a cephalic-to-caudal sequence. However, development and growth are decoupled and growth is fastest initially in the posterior presacrals and sacrum. In addition, there is a time lag between the formation of the presacral/sacral region and the postsacral region. More than 8.5% of the specimens examined have vertebral anomalies, and about 50% display small variants from the typical vertebral column morphology. However, these malformations do not seem to have been so severe as to have affected survival. PMID:18946872

  15. Loss of laminin alpha 1 results in multiple structural defects and divergent effects on adhesion during vertebrate optic cup morphogenesis.

    PubMed

    Bryan, Chase D; Chien, Chi-Bin; Kwan, Kristen M

    2016-08-15

    The vertebrate eye forms via a complex set of morphogenetic events. The optic vesicle evaginates and undergoes transformative shape changes to form the optic cup, in which neural retina and retinal pigmented epithelium enwrap the lens. It has long been known that a complex, glycoprotein-rich extracellular matrix layer surrounds the developing optic cup throughout the process, yet the functions of the matrix and its specific molecular components have remained unclear. Previous work established a role for laminin extracellular matrix in particular steps of eye development, including optic vesicle evagination, lens differentiation, and retinal ganglion cell polarization, yet it is unknown what role laminin might play in the early process of optic cup formation subsequent to the initial step of optic vesicle evagination. Here, we use the zebrafish lama1 mutant (lama1(UW1)) to determine the function of laminin during optic cup morphogenesis. Using live imaging, we find, surprisingly, that loss of laminin leads to divergent effects on focal adhesion assembly in a spatiotemporally-specific manner, and that laminin is required for multiple steps of optic cup morphogenesis, including optic stalk constriction, invagination, and formation of a spherical lens. Laminin is not required for single cell behaviors and changes in cell shape. Rather, in lama1(UW1) mutants, loss of epithelial polarity and altered adhesion lead to defective tissue architecture and formation of a disorganized retina. These results demonstrate that the laminin extracellular matrix plays multiple critical roles regulating adhesion and polarity to establish and maintain tissue structure during optic cup morphogenesis. PMID:27339294

  16. An overview of vertebrate mineralization with emphasis on collagen-mineral interaction.

    PubMed

    Landis, W J

    1999-05-01

    The nucleation, growth, and development of mineral crystals through their interaction principally with collagen in normal bone and calcifying tendon have been elaborated by applying a number of different techniques for analysis of the inorganic and organic constituents of these tissues. The methods have included conventional and high voltage electron microscopy, electron diffraction, microscopic tomography and 3D image reconstruction, and atomic force microscopy. This summary presents results of these studies that have now characterized the size, shape, and aspects of the chemical nature of the crystals as well as their orientation, alignment, location, and distribution with respect to collagen. These data have provided the means for understanding more completely the formation and strength of the collagen-mineral composite present in most vertebrate calcifying tissues and, from that information, a basis for the adaptation of such tissues under mechanical constraints. In the context of the latter point, other data are given showing effects on collagen in bone cell cultures subjected to the unloading parameters of spaceflight. Implications of these results may be particularly relevant to explaining loss of bone by humans and other vertebrate animals during missions in space, during situations of extended fracture healing, long-term bedrest, physical immobilization, and related conditions. In a broader sense, the data speak to the response of bone and mineralized vertebrate tissues to changes in gravitational loading and applied mechanical forces in general. PMID:11541779

  17. An overview of vertebrate mineralization with emphasis on collagen-mineral interaction

    NASA Technical Reports Server (NTRS)

    Landis, W. J.

    1999-01-01

    The nucleation, growth, and development of mineral crystals through their interaction principally with collagen in normal bone and calcifying tendon have been elaborated by applying a number of different techniques for analysis of the inorganic and organic constituents of these tissues. The methods have included conventional and high voltage electron microscopy, electron diffraction, microscopic tomography and 3D image reconstruction, and atomic force microscopy. This summary presents results of these studies that have now characterized the size, shape, and aspects of the chemical nature of the crystals as well as their orientation, alignment, location, and distribution with respect to collagen. These data have provided the means for understanding more completely the formation and strength of the collagen-mineral composite present in most vertebrate calcifying tissues and, from that information, a basis for the adaptation of such tissues under mechanical constraints. In the context of the latter point, other data are given showing effects on collagen in bone cell cultures subjected to the unloading parameters of spaceflight. Implications of these results may be particularly relevant to explaining loss of bone by humans and other vertebrate animals during missions in space, during situations of extended fracture healing, long-term bedrest, physical immobilization, and related conditions. In a broader sense, the data speak to the response of bone and mineralized vertebrate tissues to changes in gravitational loading and applied mechanical forces in general.

  18. 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

  19. Sox11 Is Required to Maintain Proper Levels of Hedgehog Signaling during Vertebrate Ocular Morphogenesis

    PubMed Central

    Pillai-Kastoori, Lakshmi; Wen, Wen; Wilson, Stephen G.; Strachan, Erin; Lo-Castro, Adriana; Fichera, Marco; Musumeci, Sebastiano A.; Lehmann, Ordan J.; Morris, Ann C.

    2014-01-01

    Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC) and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders. PMID:25010521

  20. Stripes and belly-spots -- a review of pigment cell morphogenesis in vertebrates.

    PubMed

    Kelsh, Robert N; Harris, Melissa L; Colanesi, Sarah; Erickson, Carol A

    2009-02-01

    Pigment patterns in the integument have long-attracted attention from both scientists and non-scientists alike since their natural attractiveness combines with their excellence as models for the general problem of pattern formation. Pigment cells are formed from the neural crest and must migrate to reach their final locations. In this review, we focus on our current understanding of mechanisms underlying the control of pigment cell migration and patterning in diverse vertebrates. The model systems discussed here - chick, mouse, and zebrafish - each provide unique insights into the major morphogenetic events driving pigment pattern formation. In birds and mammals, melanoblasts must be specified before they can migrate on the dorsolateral pathway. Transmembrane receptors involved in guiding them onto this route include EphB2 and Ednrb2 in chick, and Kit in mouse. Terminal migration depends, in part, upon extracellular matrix reorganization by ADAMTS20. Invasion of the ectoderm, especially into the feather germ and hair follicles, requires specific signals that are beginning to be characterized. We summarize our current understanding of the mechanisms regulating melanoblast number and organization in the epidermis. We note the apparent differences in pigment pattern formation in poikilothermic vertebrates when compared with birds and mammals. With more pigment cell types, migration pathways are more complex and largely unexplored; nevertheless, a role for Kit signaling in melanophore migration is clear and indicates that at least some patterning mechanisms may be highly conserved. We summarize the multiple factors thought to contribute to zebrafish embryonic pigment pattern formation, highlighting a recent study identifying Sdf1a as one factor crucial for regulation of melanophore positioning. Finally, we discuss the mechanisms generating a second, metamorphic pigment pattern in adult fish, emphasizing recent studies strengthening the evidence that undifferentiated

  1. Comparison of vertebral and femoral bone mineral density in adult females

    PubMed Central

    Choe, Han Seong; Lee, Jae Hong; Min, Dong Ki; Shin, So Hong

    2016-01-01

    [Purpose] This study assessed vertebral and femoral bone mineral density in adult females. [Subjects and Methods] A total of 314 females in their 40s to 70s were divided into normal, osteopenia, and osteoporosis groups and their vertebral and femoral bone mineral densities were compared. [Results] Comparisons of T scores revealed significant differences among measurements of the third lumbar vertebra, femoral neck, Ward’s triangle, and femoral trochanter. Pearson correlation coefficients were used to assess differences between the vertebral and femoral measurements, and significant differences and positive correlations were observed among third lumbar vertebra, femoral neck, Ward’s triangle, and femur trochanter in the normal group. [Conclusion] Females in the normal, osteopenia, and osteoporosis groups showed significant differences in their third lumbar vertebrae. The lack of significant differences among measurements in the osteoporosis group in this study suggests that patients with osteoporosis require careful and accurate diagnosis. PMID:27390449

  2. Comparison of vertebral and femoral bone mineral density in adult females.

    PubMed

    Choe, Han Seong; Lee, Jae Hong; Min, Dong Ki; Shin, So Hong

    2016-06-01

    [Purpose] This study assessed vertebral and femoral bone mineral density in adult females. [Subjects and Methods] A total of 314 females in their 40s to 70s were divided into normal, osteopenia, and osteoporosis groups and their vertebral and femoral bone mineral densities were compared. [Results] Comparisons of T scores revealed significant differences among measurements of the third lumbar vertebra, femoral neck, Ward's triangle, and femoral trochanter. Pearson correlation coefficients were used to assess differences between the vertebral and femoral measurements, and significant differences and positive correlations were observed among third lumbar vertebra, femoral neck, Ward's triangle, and femur trochanter in the normal group. [Conclusion] Females in the normal, osteopenia, and osteoporosis groups showed significant differences in their third lumbar vertebrae. The lack of significant differences among measurements in the osteoporosis group in this study suggests that patients with osteoporosis require careful and accurate diagnosis. PMID:27390449

  3. Material properties and biochemical composition of mineralized vertebral cartilage in seven elasmobranch species (Chondrichthyes).

    PubMed

    Porter, Marianne E; Beltrán, Jennie L; Koob, Thomas J; Summers, Adam P

    2006-08-01

    Elasmobranchs, particularly sharks, function at speed and size extremes, exerting large forces on their cartilaginous skeletons while swimming. This casts doubt on the generalization that cartilaginous skeletons are mechanically inferior to bony skeletons, a proposition that has never been experimentally verified. We tested mineralized vertebral centra from seven species of elasmobranch fishes: six sharks and one axially undulating electric ray. Species were chosen to represent a variety of morphologies, inferred swimming speeds and ecological niches. We found vertebral cartilage to be as stiff and strong as mammalian trabecular bone. Inferred swimming speed was a good, but not infallible, predictor of stiffness and strength. Collagen content was also a good predictor of material stiffness and strength, although proteoglycan was not. The mineral fraction in vertebral cartilage was similar to that in mammalian trabecular bone and was a significant predictor of material properties. PMID:16857876

  4. Mineralization and collagen orientation throughout aging at the vertebral endplate in the human lumbar spine.

    PubMed

    Paietta, Rachel C; Burger, Evalina L; Ferguson, Virginia L

    2013-11-01

    The human vertebral body and intervertebral disc interface forms the region where the cartilaginous endplate, annulus fibrosis and bone of the vertebral body are connected through an intermediate calcified cartilage layer. While properties of both the vertebral body and components of the disc have been extensively studied, limited quantitative data exists describing the microstructure of the vertebral body-intervertebral disc interface in the spine throughout development and degeneration. Quantitative backscattered scanning electron and second harmonic generation confocal imaging were used to collect quantitative data describing the mineral content and collagen fiber orientation across the interface, respectively. Specimens spanned ages 56 days to 84 years and measurements were taken across the vertebral endplate at the outer annulus, inner annulus and nucleus pulposis. In mature and healthy endplates, collagen fibers span the calcified cartilage layer in all regions, including the endplate adjacent to the central nucleus pulposis. We also observed an abrupt transition from high mineral volume fractions (35-50%) to 0% over short distances measuring 3-15 microns in width across the transition from calcified cartilage to unmineralized cartilage. The alignment of collagen fibers at the outer annulus and thickness of the CC layer indicated that collagen fiber mineralization adjacent to the bone may serve to anchor the soft tissue without a gradual change in material properties. Combining backscattered scanning electron microscopy and second harmonic generation imaging on the same sections thus enable a novel assessment of morphology and properties in both mineralized and soft tissues at the vertebral body-intervertebral disc throughout development and aging. PMID:23999190

  5. Sustained swimming increases the mineral content and osteocyte density of salmon vertebral bone

    PubMed Central

    Totland, Geir K; Fjelldal, Per Gunnar; Kryvi, Harald; Løkka, Guro; Wargelius, Anna; Sagstad, Anita; Hansen, Tom; Grotmol, Sindre

    2011-01-01

    This study addresses the effects of increased mechanical load on the vertebral bone of post-smolt Atlantic salmon by forcing them to swim at controlled speeds. The fish swam continuously in four circular tanks for 9 weeks, two groups at 0.47 body lengths (bl) × s−1 (non-exercised group) and two groups at 2 bl × s−1 (exercised group), which is just below the limit for maximum sustained swimming speed in this species. Qualitative data concerning the vertebral structure were obtained from histology and electron microscopy, and quantitative data were based on histomorphometry, high-resolution X-ray micro-computed tomography images and analysis of bone mineral content, while the mechanical properties were tested by compression. Our key findings are that the bone matrix secreted during sustained swimming had significantly higher mineral content and mechanical strength, while no effect was detected on bone in vivo architecture. mRNA levels for two mineralization-related genes bgp and alp were significantly upregulated in the exercised fish, indicating promotion of mineralization. The osteocyte density of the lamellar bone of the amphicoel was also significantly higher in the exercised than non-exercised fish, while the osteocyte density in the cancellous bone was similar in the two groups. The vertebral osteocytes did not form a functional syncytium, which shows that salmon vertebral bone responds to mechanical loading in the absence of an extensive connecting syncytial network of osteocytic cell processes as found in mammals, indicating the existence of a different mechanosensing mechanism. The adaptive response to increased load is thus probably mediated by osteoblasts or bone lining cells, a system in which signal detection and response may be co-located. This study offers new insight into the teleost bone biology, and may have implications for maintaining acceptable welfare for farmed salmon. PMID:21615400

  6. Aboveground vertebrate and invertebrate herbivore impact on net N mineralization in subalpine grasslands.

    PubMed

    Risch, Anita C; Schotz, Martin; Vandegehuchte, Martijn L; Van Der Putten, Wim H; Duyts, Henk; Raschein, Ursina; Gwiazdowicz, Dariusz J; Busse, Matt D; Page-dumroese, Deborah S; Zimmermann, Stephan

    2015-12-01

    Aboveground herbivores have strong effects on grassland nitrogen (N) cycling. They can accelerate or slow down soil net N mineralization depending on ecosystem productivity and grazing intensity. Yet, most studies only consider either ungulates or invertebrate herbivores, but not the combined effect of several functionally different vertebrate and invertebrate herbivore species or guilds. We assessed how a diverse herbivore community affects net N mineralization in subalpine grasslands. By using size-selective fences, we progressively excluded large, medium, and small mammals, as well as invertebrates from two vegetation types, and assessed how the exclosure types (ET) affected net N mineralization. The two vegetation types differed in long-term management (centuries), forage quality, and grazing history and intensity. To gain a more mechanistic understanding of how herbivores affect net N mineralization, we linked mineralization to soil abiotic (temperature; moisture; NO3-, NH4+, and total inorganic N concentrations/pools; C, N, P concentrations; pH; bulk density), soil biotic (microbial biomass; abundance of collembolans, mites, and nematodes) and plant (shoot and root biomass; consumption; plant C, N, and fiber content; plant N pool) properties. Net N mineralization differed between ET, but not between vegetation types. Thus, short-term changes in herbivore community composition and, therefore, in grazing intensity had a stronger effect on net N mineralization than long-term management and grazing history. We found highest N mineralization values when only invertebrates were present, suggesting that mammals had a negative effect on net N mineralization. Of the variables included in our analyses, only mite abundance and aboveground plant biomass explained variation in net N mineralization among ET. Abundances of both mites and leaf-sucking invertebrates were positively correlated with aboveground plant biomass, and biomass increased with progressive exclusion

  7. Thoracic and lumbar vertebral bone mineral density changes in a natural occurring dog model of diffuse idiopathic skeletal hyperostosis.

    PubMed

    De Decker, Steven; Lam, Richard; Packer, Rowena M A; Gielen, Ingrid M V L; Volk, Holger A

    2015-01-01

    Ankylosing spinal disorders can be associated with alterations in vertebral bone mineral density (BMD). There is however controversy about vertebral BMD in patients wuse idiopathic skeletal hyperostosis (DISH). DISH in Boxer dogs has been considered a natural occurring disease model for DISH in people. The purpose of this study was to compare vertebral BMD between Boxers with and without DISH. Fifty-nine Boxers with (n=30) or without (n=29) DISH that underwent computed tomography were included. Vertebral BMD was calculated for each thoracic and lumbar vertebra by using an earlier reported and validated protocol. For each vertebral body, a region of interest was drawn on the axial computed tomographic images at three separate locations: immediately inferior to the superior end plate, in the middle of the vertebral body, and superior to the inferior end plate. Values from the three axial slices were averaged to give a mean Hounsfield Unit value for each vertebral body. Univariate statistical analysis was performed to identify factors to be included in a multivariate model. The multivariate model including all dogs demonstrated that vertebral DISH status (Coefficient 24.63; 95% CI 16.07 to 33.19; p <0.001), lumbar vertebrae (Coefficient -17.25; 95% CI -23.42 to -11.09; p < 0.01), and to a lesser extent higher age (Coefficient -0.56; 95% CI -1.07 to -0.05; p = 0.03) were significant predictors for vertebral BMD. When the multivariate model was repeated using only dogs with DISH, vertebral DISH status (Coefficient 20.67; 95% CI, 10.98 to 30.37; p < 0.001) and lumbar anatomical region (Coefficient -38.24; 95% CI, -47.75 to -28.73; p < 0.001) were again predictors for vertebral BMD but age was not. The results of this study indicate that DISH can be associated with decreased vertebral BMD. Further studies are necessary to evaluate the clinical importance and pathophysiology of this finding. PMID:25898128

  8. Thoracic and Lumbar Vertebral Bone Mineral Density Changes in a Natural Occurring Dog Model of Diffuse Idiopathic Skeletal Hyperostosis

    PubMed Central

    De Decker, Steven; Lam, Richard; Packer, Rowena M. A.; Gielen, Ingrid M. V. L.; Volk, Holger A.

    2015-01-01

    Ankylosing spinal disorders can be associated with alterations in vertebral bone mineral density (BMD). There is however controversy about vertebral BMD in patients wuse idiopathic skeletal hyperostosis (DISH). DISH in Boxer dogs has been considered a natural occurring disease model for DISH in people. The purpose of this study was to compare vertebral BMD between Boxers with and without DISH. Fifty-nine Boxers with (n=30) or without (n=29) DISH that underwent computed tomography were included. Vertebral BMD was calculated for each thoracic and lumbar vertebra by using an earlier reported and validated protocol. For each vertebral body, a region of interest was drawn on the axial computed tomographic images at three separate locations: immediately inferior to the superior end plate, in the middle of the vertebral body, and superior to the inferior end plate. Values from the three axial slices were averaged to give a mean Hounsfield Unit value for each vertebral body. Univariate statistical analysis was performed to identify factors to be included in a multivariate model. The multivariate model including all dogs demonstrated that vertebral DISH status (Coefficient 24.63; 95% CI 16.07 to 33.19; p <0.001), lumbar vertebrae (Coefficient -17.25; 95% CI -23.42 to -11.09; p < 0.01), and to a lesser extent higher age (Coefficient -0.56; 95% CI -1.07 to -0.05; p = 0.03) were significant predictors for vertebral BMD. When the multivariate model was repeated using only dogs with DISH, vertebral DISH status (Coefficient 20.67; 95% CI, 10.98 to 30.37; p < 0.001) and lumbar anatomical region (Coefficient -38.24; 95% CI, -47.75 to -28.73; p < 0.001) were again predictors for vertebral BMD but age was not. The results of this study indicate that DISH can be associated with decreased vertebral BMD. Further studies are necessary to evaluate the clinical importance and pathophysiology of this finding. PMID:25898128

  9. Strontium increases vertebral bone volume in rats at a low dose that does not induce detectable mineralization defect.

    PubMed

    Grynpas, M D; Hamilton, E; Cheung, R; Tsouderos, Y; Deloffre, P; Hott, M; Marie, P J

    1996-03-01

    Low doses of strontium and fluoride were shown to increase bone formation and trabecular bone density in rodents. To assess whether strontium or fluoride affect the quality of the mineral at doses known to increase bone density, we have determined the effects of low doses of strontium and fluoride on bone formation and bone mineral characteristics in rats. Adult rats were given strontium alone (0.20%), fluoride alone (1 mg/kg per day), or the combined treatment for 8 weeks. Strontium levels in serum and femur were similar in groups treated with strontium alone or in combination, being about 5% of calcium levels. Biochemical and neutron activation analyses in femur showed that calcium and magnesium contents did not differ in the four group of rats, suggesting that strontium was incorporated in the apatite lattice of the bone minerals in the strontium-treated rats. The mineralized bone volume was significantly increased by 17% in the strontium-treated group, by 20% in the fluoride-treated group, and by 19% in rats given with the combined treatment. This was associated with increased osteoid surface, osteoblast surface, and double tetracycline labeled surfaces in the strontium-treated and fluoride-treated groups, showing that the number of bone forming sites was increased. However, the mineral apposition rate, the osteoid thickness, and the mineralization lag time were similar in controls and treated groups, reflecting the lack of deleterious effects of low doses of strontium and fluoride on bone mineralization. The density fractionation analysis measured in the femur also showed that neither strontium, nor fluoride at the low doses used, significantly altered the mineralization profile. The results indicate that treatment with low doses of strontium or fluoride increase the number of bone forming sites and vertebral bone volume in rats, but does not have detectable adverse effects on the mineral profile, bone mineral chemistry or bone matrix mineralization. PMID

  10. Developing pressures: fluid forces driving morphogenesis.

    PubMed

    Navis, Adam; Bagnat, Michel

    2015-06-01

    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

  11. Microscale Material Properties of Bone and the Mineralized Tissues of the Intervertebral Disc-Vertebral Body Interface

    NASA Astrophysics Data System (ADS)

    Paietta, Rachel C.

    The objective of this dissertation is to understand the influences of material structure on the properties, function and failure of biological connective tissues. Biological interfaces are becoming an increasingly studied system within mechanics and tissue engineering as a model for attaching dissimilar materials. The elastic modulus of bone (≈ 20 GPa) and cartilage (≈ 0.1-1 MPa) differ over orders of magnitude, which should intuitively create high stress concentrations and failure at the interface. Yet, these natural interface systems rarely fail in vivo, and the mechanism by which loads are transferred between tissues has not yet been established. Tissue quality is one major contributor to the mechanical behavior of bone and cartilage, and is defined by properties such as collagen orientation, mineral volume fraction, porosity and tissue geometry. These properties have yet to be established at the bone-cartilage interface in the spine, and the lack of quantitative data on material microstructure and behavior limits treatments and tissue engineering construct design. In this dissertation, second harmonic generation imaging, quantitative backscattered scanning electron imaging and nanoindentation are combined to characterize micrometer scale tissue quality and modulus in both bone and calcified cartilage. These techniques are utilized to: 1) determine the hierarchical micrometer to millimeter scale properties of lamellar bone, 2) quantify changes throughout development and aging at the human intervertebral disc-vertebral body junction, and 3) explore compressive fractures at this interface. This work is the first to provide quantitative data on the mineral volume fraction, collagen orientation and modulus from the same, undecalcified sections of tissue to corroborate tissue structure and mineralization and describe quantitative parameters of the interface. The principal findings from this work indicate that the underlying matrix, or collagen, organization in

  12. Cervical Vertebral Trabecular Bone Mineral Density in Great Danes With and Without Osseous-Associated Cervical Spondylomyelopathy

    PubMed Central

    Armstrong, J.; da Costa, R.C.; Martin-Vaquero, P.

    2015-01-01

    Background Great Danes (GDs) with osseous-associated cervical spondylomyelopathy (CSM) have osteoarthritis (OA) of the cervical vertebrae. OA is often associated with increases in bone mineral density (BMD) in people and dogs. Hypothesis/Objectives To compare the trabecular BMD of the cervical vertebrae between clinically normal (control) GDs and GDs with osseous-associated CSM by using computed tomography (CT). We hypothesized that the vertebral trabecular BMD of CSM-affected GDs would be higher than that of control GDs. Animals Client-owned GDs: 12 controls, 10 CSM affected. Methods Prospective study. CT of the cervical vertebral column was obtained alongside a calibration phantom. By placing a circular region of interest at the articular process joints, vertebral body, pedicles, and within each rod of the calibration phantom, trabecular BMD was measured in Hounsfield units, which were converted to diphosphate equivalent densities. Trabecular BMD measurements were compared between CSM-affected and control dogs, and between males and females within the control group. Results Differences between CSM-affected and control dogs were not significant for the articular processes (mean = −39; P = .37; 95% CI: −102 to 24), vertebral bodies (mean = −62; P = .08; 95% CI: −129 to 6), or pedicles (mean = −36; P = .51; 95% CI: −105 to 33). Differences between female and male were not significant. Conclusions and Clinical Importance This study revealed no difference in BMD between control and CSM-affected GDs. Based on our findings no association was detected between cervical OA and BMD in GDs with CSM. PMID:25312453

  13. Minodronic acid ameliorates vertebral bone strength by increasing bone mineral density in 9-month treatment of ovariectomized cynomolgus monkeys.

    PubMed

    Tanaka, Makoto; Mori, Hiroshi; Kawabata, Kazuhito; Mashiba, Tasuku

    2016-07-01

    The effect of treatment for 9months with minodronic acid, a nitrogen-containing bisphosphonate, on vertebral mechanical strength was examined in ovariectomized (OVX) cynomolgus monkeys. Forty skeletally mature female monkeys were randomized into four OVX groups and one sham group (n=8) based on lumbar bone mineral density (BMD). OVX animals were treated orally with 15 and 150μg/kg QD of minodronic acid or 500μg/kg QD alendronate as a reference drug. Measurements of bone turnover markers and lumbar BMD were conducted at 0, 4 and 8months. Measurements of bone mechanical strength and minodronic acid concentration in vertebral bodies were also performed. OVX resulted in a decrease in lumbar BMD and an increase in bone turnover markers at 4 and 8months, compared to the sham group, and the ultimate load on the lumbar vertebra was decreased in OVX animals. Minodronic acid and alendronate prevented the OVX-induced increase in bone turnover markers and decrease in lumbar BMD. Minodronic acid at 150μg/kg increased the ultimate load on lumbar vertebra compared to untreated OVX animals. Regression analysis revealed that the ultimate load was correlated with lumbar BMD and bone mineral content (BMC), and most strongly with the increase in lumbar BMD and BMC over 8months. In a separate analysis within the sham-OVX controls and minodronic acid and alendronate treatment groups, the ultimate loads were also correlated with BMD and BMC. The load-BMD (BMC) correlation in the minodronic acid group showed a trend for a shift to a higher load from the basal relationship in the sham-OVX controls. These results indicate that treatment with minodronic acid for 9months increases vertebral mechanical strength in OVX monkeys, mainly by increasing BMD and BMC. PMID:27155564

  14. Cooption of secretory phospholipase (SPLA2) for different aspects of gravity receptor-associated mineralization in vertebrate phylogeny

    NASA Astrophysics Data System (ADS)

    Thalmann, R.; Lu, W.

    2009-04-01

    Vertebrate gravity-associated minerals consists of either a single large stone (otolith), or an assembly of minute biomineral particles, otoconia ("ear dust"). Otoliths and both, amphibian and reptilian otoconia, consist of aragonite, whereas avian and mammalian otoconia consist of calcite. Vertebrate gravity-associated minerals are the product of site-directed biologically-controlled mineralization. Insoluble frame work molecules specify sites of nucleation and direction of crystal growth. Soluble matrix proteins modulate growth kinetics and crystal morphology. It is most remarkable that the principal insoluble frame work protein, otolin, is the same for both, otolith and otoconia. Otolin is a novel type of collagen, homologous to the network-forming collagen type X prevalent in mature chondrocytes. The principal soluble matrix proteins of calcitic, aragonitic, and most likely also of vateritic otoconia are all homologs of SPLA2, which is most prevalent in pancreatic secretion and snake venoms. Otonin90 (OC90), the principal soluble matrix protein of calcitic otoconia consists of two SPLA-like (SPLAL) domains, which are connected by a sizeable linker segment and contain significant terminal extensions. The MW of the protein backbone amounts to approximately 50 kDa. The molecule contains, in addition massive post-translational modifications, 80% of which are accounted for by sulfated GAGs, resulting in a total MW of 100 KDa. The protein backbone is moderately acidic, pI 4.4, but the pI of the whole molecule is 2.9, indicating a substantial acidity of the GAG component. In adapting SPLA2 for mineral modulation the enzymatic site is modified and presumed nonfunctional. The seven SH- bonds are rigorously conserved in both, OC90 and otoconin22 (OC22). It appears that the SH-bonds of the parent SPLA2 are intended to stabilize the molecule to ensure continued enzymatic activity in the hostile environment of the gut. It therefore seems logical that SPLA2 was coopted for

  15. Higher Level of Dickkopf-1 is Associated with Low Bone Mineral Density and Higher Prevalence of Vertebral Fractures in Patients with Ankylosing Spondylitis.

    PubMed

    Rossini, Maurizio; Viapiana, Ombretta; Idolazzi, Luca; Ghellere, Francesco; Fracassi, Elena; Troplini, Sonila; Povino, Maria Rosaria; Kunnathully, Vidya; Adami, Silvano; Gatti, Davide

    2016-05-01

    Patients with ankylosing spondylitis (AS) have an increased risk of bone loss and vertebral fractures. In this study, we explored the hypothesis that the excess bone loss and vertebral fractures might be related with the activity of the Wingless signaling pathway, and in particular with the serum levels of its circulating inhibitors, Sclerostin and Dickkopf-1 (DKK1). We recruited 71 patients diagnosed with AS. Lateral radiographs of the total spine were analyzed to detect the presence of vertebral fractures, and bone mineral density (BMD) was assessed in all patients using dual X-ray absorptiometry at lumbar spine and proximal femoral site. Blood samples were obtained and levels of C-reactive protein (CRP), DKK1, and Sclerostin were measured. Blood samples from 71 healthy sex- and age-matched volunteers were collected to be used as controls. Vertebral fractures were detected more commonly among men than in women (29 vs 8 %, respectively). DKK1, but not Sclerostin serum levels, were inversely correlated to lumbar spine Z-score BMD. Patients with one or more prevalent vertebral fractures had significantly higher DKK1 levels, without significant difference in Sclerostin serum levels. A significant positive correlation was found between DKK1 serum levels and CRP (r = 0.240, p = 0.043). The association we found between serum DKK1 levels and BMD values and vertebral fracture prevalence suggests that DKK1 might contribute to the severity of osteoporosis in AS. PMID:26645432

  16. Picornavirus Morphogenesis

    PubMed Central

    Jiang, Ping; Liu, Ying; Ma, Hsin-Chieh; Paul, Aniko V.

    2014-01-01

    SUMMARY The Picornaviridae represent a large family of small plus-strand RNA viruses that cause a bewildering array of important human and animal diseases. Morphogenesis is the least-understood step in the life cycle of these viruses, and this process is difficult to study because encapsidation is tightly coupled to genome translation and RNA replication. Although the basic steps of assembly have been known for some time, very few details are available about the mechanism and factors that regulate this process. Most of the information available has been derived from studies of enteroviruses, in particular poliovirus, where recent evidence has shown that, surprisingly, the specificity of encapsidation is governed by a viral protein-protein interaction that does not involve an RNA packaging signal. In this review, we make an attempt to summarize what is currently known about the following topics: (i) encapsidation intermediates, (ii) the specificity of encapsidation (iii), viral and cellular factors that are required for encapsidation, (iv) inhibitors of encapsidation, and (v) a model of enterovirus encapsidation. Finally, we compare some features of picornavirus morphogenesis with those of other plus-strand RNA viruses. PMID:25184560

  17. Cooption of secretory phospholipase (SPLA2) for different aspects of gravity receptor-associated mineralization in vertebrate phylogeny

    NASA Astrophysics Data System (ADS)

    Thalmann, R.; Lu, W.

    2009-04-01

    Vertebrate gravity-associated minerals consists of either a single large stone (otolith), or an assembly of minute biomineral particles, otoconia ("ear dust"). Otoliths and both, amphibian and reptilian otoconia, consist of aragonite, whereas avian and mammalian otoconia consist of calcite. Vertebrate gravity-associated minerals are the product of site-directed biologically-controlled mineralization. Insoluble frame work molecules specify sites of nucleation and direction of crystal growth. Soluble matrix proteins modulate growth kinetics and crystal morphology. It is most remarkable that the principal insoluble frame work protein, otolin, is the same for both, otolith and otoconia. Otolin is a novel type of collagen, homologous to the network-forming collagen type X prevalent in mature chondrocytes. The principal soluble matrix proteins of calcitic, aragonitic, and most likely also of vateritic otoconia are all homologs of SPLA2, which is most prevalent in pancreatic secretion and snake venoms. Otonin90 (OC90), the principal soluble matrix protein of calcitic otoconia consists of two SPLA-like (SPLAL) domains, which are connected by a sizeable linker segment and contain significant terminal extensions. The MW of the protein backbone amounts to approximately 50 kDa. The molecule contains, in addition massive post-translational modifications, 80% of which are accounted for by sulfated GAGs, resulting in a total MW of 100 KDa. The protein backbone is moderately acidic, pI 4.4, but the pI of the whole molecule is 2.9, indicating a substantial acidity of the GAG component. In adapting SPLA2 for mineral modulation the enzymatic site is modified and presumed nonfunctional. The seven SH- bonds are rigorously conserved in both, OC90 and otoconin22 (OC22). It appears that the SH-bonds of the parent SPLA2 are intended to stabilize the molecule to ensure continued enzymatic activity in the hostile environment of the gut. It therefore seems logical that SPLA2 was coopted for

  18. Usefulness of Fracture Risk Assessment Tool Using Lumbar Bone Mineral Density in Prediction of Osteoporotic Vertebral Fracture

    PubMed Central

    Lee, Heui Seung; Lee, Sang Hyung; Chung, Young Seob; Yang, Hee-Jin; Son, Young-Je

    2015-01-01

    Objective To investigate the value of lumbar bone mineral density (BMD) in fracture risk assessment (FRAX) tool. Methods One hundred and ten patients aged over 60 years were enrolled and divided into 2 groups as non-osteoporotic vertebral fracture (OVF) and OVF groups. The 10-year-risk of major osteoporotic vertebral fracture of each group was calculated by FRAX tool with femoral and lumbar spine BMDs to compare the usefulness of lumbar spine BMD in prediction of OVF. The blood level of osteocalcin and C-terminal telopeptide (CTX) as markers of activities of osteoblast and osteoclast, respectively were analyzed using the institutional database. Results In the OVF group, the ratio of patients with previous fracture history or use of glucocorticoid was higher than those in non-OVF group (p=0.000 and 0.030, respectively). The levels of T-score of femur neck and lumbar spine in OVF group were significantly lower than those in non-OVF group (p=0.001 and 0.000, respectively). The risk of OVF in FRAX using femur BMD in non-OVF and OVF groups was 6.7±6.13 and 11.4±10.06, respectively (p=0.007). The risk of using lumbar BMD in the 2 groups was 6.9±8.91 and 15.1±15.08, respectively (p=0.002). The areas under the receiver operator characteristic curve in the FRAX risk with lumbar and femur neck BMD were 0.726 and 0.684, respectively. The comparison of osteocalcin and CTX was not significant (p=0.162 and 0.369, respectively). Conclusion In our study, the 10-year risk of major osteoporotic fracture in the OVF group of our study was lower than the recommended threshold of intervention for osteoporosis. Hence, a lower threshold for the treatment of osteoporosis may be set for the Korean population to prevent OVF. In the prediction of symptomatic OVF, FRAX tool using lumbar spine BMD may be more useful than that using femur neck BMD. PMID:26587188

  19. Histological evaluation of an impacted bone graft substitute composed of a combination of mineralized and demineralized allograft in a sheep vertebral bone defect.

    PubMed

    Fujishiro, Takaaki; Bauer, Thomas W; Kobayashi, Naomi; Kobayashi, Hideo; Sunwoo, Moon Hae; Seim, Howard B; Turner, A Simon

    2007-09-01

    Demineralized bone matrix (DBMs) preparations are a potential alternative or supplement to autogenous bone graft, but many DBMs have not been adequately tested in clinically relevant animal models. The aim of current study was to compare the efficacy of a new bone graft substitute composed of a combination of mineralized and demineralized allograft, along with hyaluronic acid (AFT Bone Void Filler) with several other bone graft materials in a sheep vertebral bone void model. A drilled defect in the sheep vertebral body was filled with either the new DBM preparation, calcium sulfate (OsteoSet), autologous bone graft, or left empty. The sheep were euthanized after 6 or 12 weeks, and the defects were examined by histology and quantitative histomorphometry. The morphometry data were analyzed by one-way analysis of variance with the post hoc Tukey-Kramer test or the Student's t-test. All of the bone defects in the AFT DBM preparation group showed good new bone formation with variable amounts of residual DBM and mineralized bone graft. The DBM preparation group at 12 weeks contained significantly more new bone than the defects treated with calcium sulfate or left empty (respectively, p < 0.05, p < 0.01). There was no significant difference between the DBM and autograft groups. No adverse inflammatory reactions were associated with any of the three graft materials. The AFT preparation of a mixture of mineralized and demineralized allograft appears to be an effective autograft substitute as tested in this sheep vertebral bone void model. PMID:17309059

  20. The Choice of Normative Pediatric Reference Database Changes Spine Bone Mineral Density Z-scores But Not The Relationship Between Bone Mineral Density and Prevalent Vertebral Fractures

    PubMed Central

    Ma, Jinhui; Siminoski, Kerry; Alos, Nathalie; Halton, Jacqueline; Ho, Josephine; Lentle, Brian; Matzinger, MaryAnn; Shenouda, Nazih; Atkinson, Stephanie; Barr, Ronald; Cabral, David A.; Couch, Robert; Cummings, Elizabeth A.; Fernandez, Conrad V.; Grant, Ronald M.; Rodd, Celia; Sbrocchi, Anne Marie; Scharke, Maya; Rauch, Frank; Ward, Leanne M.

    2015-01-01

    Objectives Our objectives were to assess the magnitude of the disparity in lumbar spine bone mineral density (LSBMD) Z-scores generated by different reference databases and to evaluate whether the relationship between LSBMD Z-scores and vertebral fractures (VF) varies by choice of database. Patients and Design Children with leukemia underwent LSBMD by cross-calibrated dual energy x-ray absorptiometry, with Z-scores generated according to Hologic and Lunar databases. VF were assessed by the Genant method on spine radiographs. Logistic regression was used to assess the association between fractures and LSBMD Z-scores. Net reclassification improvement (NRI) and area under the receiver operating characteristic curve (AUC) were calculated to assess the predictive accuracy of LSBMD Z-scores for VF. Results For the 186 children from 0–18 years of age, 6 different age ranges were studied. The Z-scores generated for the 0 to 18 group were highly correlated (r ≥ 0.90), but the proportion of children with LSBMD Z-scores ≤ −2.0 among those with VF varied substantially (from 38 to 66%). Odds ratios (OR) for the association between LSBMD Z-score and VF were similar regardless of database (OR = 1.92, 95% confidence interval (CI): 1.44, 2.56 to OR = 2.70, 95% CI: 1.70, 4.28). AUC and NRI ranged from 0.71 to 0.75 and −0.15 to 0.07 respectively. Conclusions Although the use of a LSBMD Z-score threshold as part of the definition of osteoporosis in a child with VF does not appear valid, the study of relationships between BMD and VF is valid regardless of the BMD database that is used. PMID:25494661

  1. Minerals

    MedlinePlus

    Minerals are important for your body to stay healthy. Your body uses minerals for many different jobs, including building bones, making ... regulating your heartbeat. There are two kinds of minerals: macrominerals and trace minerals. Macrominerals are minerals your ...

  2. Comparison of nuclear magnetic resonance spectroscopy with dual-photon absorptiometry and dual-energy X-ray absorptiometry in the measurement of thoracic vertebral bone mineral density: compressive force versus bone mineral.

    PubMed

    Myers, T J; Battocletti, J H; Mahesh, M; Gulati, M; Wilson, C R; Pintar, F; Reinartz, J

    1994-05-01

    31P nuclear magnetic resonance spectroscopy (NMRS) measurements were made on human T2 and T3 vertebral bodies. The bone mineral content (BMC) of isolated vertebral bodies minus the posterior elements and disks was measured using (1) NMRS on a 3.5 T, 85 mm bore GE Medical Systems NT-150 superconducting spectrometer, (2) a Lunar Corporation DPX-L dual-energy X-ray absorptiometry (DXA) scanner in an anterior-posterior (AP) orientation, (3) a Norland Corporation XR26 DXA scanner, also in an AP direction, and (4) a Norland Corporation model 2600 dual-photon absorptiometry (DPA) densitometer in both the AP and superior-inferior (SI) directions. Vertebral body volumes were measured using a water displacement technique to determine volume bone mineral densities (VBMD). They were then compressed to failure using an electrohydraulic testing device, followed by ashing in a muffle furnace at 700 degrees C for 18 h. Correlations of BMC between NMRS and DPA, DXA and ashing were excellent (0.96 < or = r < or = 0.99); in a one-way analysis of variance (ANOVA) test, means were not statistically different at a p level of 0.757. The correlations of VBMD between NMRS and the other methods were not as good (0.83 < or = r < or = 0.95); in a one-way ANOVA test, means were not statistically different at a p level of 0.089. BMC was a better predictor of ultimate compressive failure than VBMD for all six methods. For NMRS, the regression coefficient for BMC was r2 = 0.806, compared with r2 = 0.505 for VBMD. NMRS may prove an alternative to present methods of determining bone mineral. PMID:8069051

  3. Mechanotransduction During Vertebrate Neurulation.

    PubMed

    Sokol, Sergei Y

    2016-01-01

    Vertebrate neural tube formation is a complex morphogenetic process, which involves hundreds of genes dynamically coordinating various behaviors in different cell populations of neural tissue. The challenge remains to determine the relative contributions of physical forces and biochemical signaling events to neural tube closure and accompanying cell fate specification. Planar cell polarity (PCP) molecules are prime candidate factors for the production of actomyosin-dependent mechanical signals necessary for morphogenesis. Conversely, physical forces may contribute to the polarized distribution of PCP proteins. Understanding mechanosensory and mechanotransducing properties of diverse molecules should help define the direction and amplitude of physical stresses that are critical for neurulation. PMID:26969989

  4. Vertebrate skeletogenesis.

    PubMed

    Lefebvre, Véronique; Bhattaram, Pallavi

    2010-01-01

    Vertebrate skeletogenesis consists in elaborating an edifice of more than 200 pieces of bone and cartilage. Each skeletal piece is crafted at a distinct location in the body, is articulated with others, and reaches a specific size, shape, and tissue composition according to both species instructions and individual determinants. This complex, customized body frame fulfills multiple essential tasks. It confers morphological features, allows controlled postures and movements, protects vital organs, houses hematopoiesis, stores minerals, and adsorbs toxins. This review provides an overview of the multiple facets of this ingenious process for experts as well as nonexperts of skeletogenesis. We explain how the developing vertebrate uses both specific and ubiquitously expressed genes to generate multipotent mesenchymal cells, specify them to a skeletogenic fate, control their survival and proliferation, and direct their differentiation into cartilage, bone, and joint cells. We review milestone discoveries made toward uncovering the intricate networks of regulatory factors that are involved in these processes, with an emphasis on signaling pathways and transcription factors. We describe numerous skeletal malformation and degeneration diseases that occur in humans as a result of mutations in regulatory genes, and explain how these diseases both help and motivate us to further decipher skeletogenic processes. Upon discussing current knowledge and gaps in knowledge in the control of skeletogenesis, we highlight ultimate research goals and propose research priorities and approaches for future endeavors. PMID:20691853

  5. 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

  6. Mineralization of the vertebral bodies in Atlantic salmon (Salmo salar L.) is initiated segmentally in the form of hydroxyapatite crystal accretions in the notochord sheath.

    PubMed

    Wang, Shou; Kryvi, Harald; Grotmol, Sindre; Wargelius, Anna; Krossøy, Christel; Epple, Mattias; Neues, Frank; Furmanek, Tomasz; Totland, Geir K

    2013-08-01

    We performed a sequential morphological and molecular biological study of the development of the vertebral bodies in Atlantic salmon (Salmo salar L.). Mineralization starts in separate bony elements which fuse to form complete segmental rings within the notochord sheath. The nucleation and growth of hydroxyapatite crystals in both the lamellar type II collagen matrix of the notochord sheath and the lamellar type I collagen matrix derived from the sclerotome, were highly similar. In both matrices the hydroxyapatite crystals nucleate and accrete on the surface of the collagen fibrils rather than inside the fibrils, a process that may be controlled by a template imposed by the collagen fibrils. Apatite crystal growth starts with the formation of small plate-like structures, about 5 nm thick, that gradually grow and aggregate to form extensive multi-branched crystal arborizations, resembling dendritic growth. The hydroxyapatite crystals are always oriented parallel to the long axis of the collagen fibrils, and the lamellar collagen matrices provide oriented support for crystal growth. We demonstrate here for the first time by means of synchroton radiation based on X-ray diffraction that the chordacentra contain hydroxyapatite. We employed quantitative real-time PCR to study the expression of key signalling molecule transcripts expressed in the cellular core of the notochord. The results indicate that the notochord not only produces and maintains the notochord sheath but also expresses factors known to regulate skeletogenesis: sonic hedgehog (shh), indian hedgehog homolog b (ihhb), parathyroid hormone 1 receptor (pth1r) and transforming growth factor beta 1 (tgfb1). In conclusion, our study provides evidence for the process of vertebral body development in teleost fishes, which is initially orchestrated by the notochord. PMID:23711083

  7. The Effect of the Lumbar Vertebral Malpositioning on Bone Mineral Density Measurements of the Lumbar Spine by Dual-Energy X-Ray Absorptiometry.

    PubMed

    Izadyar, Sina; Golbarg, Shima; Takavar, Abbas; Zakariaee, Seyed Salman

    2016-01-01

    A significant discrepancy between the results of previous human and phantoms studies is identified regarding the effects of vertebral positioning on bone mineral density (BMD) measurements. We aimed to evaluate the effects of lumbar vertebral positioning on BMD measurements by dual-energy X-ray absorptiometry in a human cadaveric spine phantom. A spine phantom was designed using L1-L4 vertebrae harvested from a 48-year-old male cadaver without coronal or sagittal deformity. The spine phantom was scanned by DEXXUM T bone densitometer in a constant scanning speed of 30 mm/s and resolution of 1.0 × 1.0 mm. BMD values were measured in a positive and negative lumbar lordosis and kyphosis tilt angles in the sagittal plane, from 0° to 35°, with 7° increments. Also BMD values were measured in axial and lateral rotations with 5° increments. Projectional dual-energy X-ray absorptiometry measurements are significantly affected by positioning of the lumbar spine, more severely affected by kyphotic curvature, but also by axial and lateral rotational scoliosis as well as lordotic curvature. Increasing the severity of lordosis and kyphosis curvatures leads to false reduction of BMD value up to 17.5% and 11.5%, respectively. Increasing the degree of lateral and axial rotational scolioses results in a false decrease in BMD measurements by up to 10.8% and 9.6%, respectively. To achieve the most accurate scanning results, error sources and abnormal positioning should be identified and minimized as much as possible. If not correctable, they should be taken into consideration while interpreting the results. PMID:26778450

  8. Mineralization of the vertebral bodies in Atlantic salmon (Salmo salar L.) is initiated segmentally in the form of hydroxyapatite crystal accretions in the notochord sheath

    PubMed Central

    Wang, Shou; Kryvi, Harald; Grotmol, Sindre; Wargelius, Anna; Krossøy, Christel; Epple, Mattias; Neues, Frank; Furmanek, Tomasz; Totland, Geir K

    2013-01-01

    We performed a sequential morphological and molecular biological study of the development of the vertebral bodies in Atlantic salmon (Salmo salar L.). Mineralization starts in separate bony elements which fuse to form complete segmental rings within the notochord sheath. The nucleation and growth of hydroxyapatite crystals in both the lamellar type II collagen matrix of the notochord sheath and the lamellar type I collagen matrix derived from the sclerotome, were highly similar. In both matrices the hydroxyapatite crystals nucleate and accrete on the surface of the collagen fibrils rather than inside the fibrils, a process that may be controlled by a template imposed by the collagen fibrils. Apatite crystal growth starts with the formation of small plate-like structures, about 5 nm thick, that gradually grow and aggregate to form extensive multi-branched crystal arborizations, resembling dendritic growth. The hydroxyapatite crystals are always oriented parallel to the long axis of the collagen fibrils, and the lamellar collagen matrices provide oriented support for crystal growth. We demonstrate here for the first time by means of synchroton radiation based on X-ray diffraction that the chordacentra contain hydroxyapatite. We employed quantitative real-time PCR to study the expression of key signalling molecule transcripts expressed in the cellular core of the notochord. The results indicate that the notochord not only produces and maintains the notochord sheath but also expresses factors known to regulate skeletogenesis: sonic hedgehog (shh), indian hedgehog homolog b (ihhb), parathyroid hormone 1 receptor (pth1r) and transforming growth factor beta 1 (tgfb1). In conclusion, our study provides evidence for the process of vertebral body development in teleost fishes, which is initially orchestrated by the notochord. PMID:23711083

  9. 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

  10. 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

  11. Minerals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fish require the same minerals or inorganic elements as terrestrial animals for tissue formation, osmoregulation and various metabolic functions. Those required in large quantities are termed macro- or major minerals and those required in small quantities are called micro- or trace minerals. Fish ca...

  12. 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.

  13. 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) ...

  14. Vertebral Morphometry.

    PubMed

    Chou, Sharon H; Vokes, Tamara

    2016-01-01

    There is as yet no agreement about the criteria by which to arrive at an imaging diagnosis of a vertebral fracture. Because high-grade fractures result in alterations in vertebral shape, 1 possible avenue of diagnosis has been to quantitate changes in vertebral shape. The result has been a variety of methods for the relative and absolute measurements of vertebral dimensions. Such measurements have also lent themselves to automated computed analysis. The number of techniques reflects the absence of any consensus about the best. The semiquantitative technique proposed by Genant has become the most widely used and has served the field well for comparative purposes. Its use in higher grade fractures has been widely endorsed, if some concepts (e.g., short vertebral height-vertebrae) are at variance with lower grades of fracturing. Vertebral morphometry may be the only recourse in high volume epidemiological and interventional studies. PMID:26349790

  15. Minerals

    MedlinePlus

    ... your body needs in larger amounts. They include calcium, phosphorus, magnesium, sodium, potassium, chloride and sulfur. Your body needs just small amounts of trace minerals. These include iron, manganese, copper, iodine, zinc, cobalt, fluoride and selenium. The best way to ...

  16. Mineral content of vertebral trabecular bone: accuracy of dual energy quantitative computed tomography evaluated against neutron activation analysis and flame atomic absorption spectrometry.

    PubMed

    Louis, O; Van den Winkel, P; Covens, P; Schoutens, A; Osteaux, M

    1994-01-01

    The goal of this study was to evaluate the accuracy of preprocessing dual energy quantitative computed tomography (QCT) for assessment of trabecular bone mineral content (BMC) in lumbar vertebrae. The BMC of 49 lumbar vertebrae taken from 16 cadavers was measured using dual energy QCT with advanced software and hardware capabilities, including an automated definition of the trabecular region of interest (ROI). The midvertebral part of each vertebral body was embedded in a polyester resin and, subsequently, an experimental ROI was cut out using a scanjet image transmission procedure and a computer-assisted milling machine in order to mimic the ROI defined on QCT. After low temperature ashing, the experimental ROIs reduced to a bone powder were submitted to either nondestructive neutron activation analysis (n = 49) or to flame atomic absorption spectrometry (n = 45). BMC obtained with neutron activation analysis was closely related (r = 0.896) to that derived from atomic absorption spectrometry, taken as the gold standard, with, however, a slight overestimation. BMC values measured by QCT were highly correlated with those assessed using the two reference methods, all correlation coefficients being > 0.841. The standard errors of the estimate ranged 47.4-58.9 mg calcium hydroxyapatite in the regressions of BMC obtained with reference methods against BMC assessed by single energy QCT, 47.1-51.9 in the regressions involving dual energy QCT. We conclude that the trabecular BMC of lumbar vertebrae can be accurately measured by QCT and that the superiority in accuracy of dual energy is moderate, which is possible a characteristic of the preprocessing method. PMID:8024849

  17. 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

  18. 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.

  19. 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

  20. Xenopus Limb bud morphogenesis.

    PubMed

    Keenan, Samuel R; Beck, Caroline W

    2016-03-01

    Xenopus laevis, the South African clawed frog, is a well-established model organism for the study of developmental biology and regeneration due to its many advantages for both classical and molecular studies of patterning and morphogenesis. While contemporary studies of limb development tend to focus on models developed from the study of chicken and mouse embryos, there are also many classical studies of limb development in frogs. These include both fate and specification maps, that, due to their age, are perhaps not as widely known or cited as they should be. This has led to some inevitable misinterpretations- for example, it is often said that Xenopus limb buds have no apical ectodermal ridge, a morphological signalling centre located at the distal dorsal/ventral epithelial boundary and known to regulate limb bud outgrowth. These studies are valuable both from an evolutionary perspective, because amphibians diverged early from the amniote lineage, and from a developmental perspective, as amphibian limbs are capable of regeneration. Here, we describe Xenopus limb morphogenesis with reference to both classical and molecular studies, to create a clearer picture of what we know, and what is still mysterious, about this process. PMID:26404044

  1. 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

  2. Marek's disease virus morphogenesis.

    PubMed

    Denesvre, Caroline

    2013-06-01

    Marek's disease virus (MDV) is a highly contagious virus that induces T-lymphoma in chicken. This viral infection still circulates in poultry flocks despite the use of vaccines. With the emergence of new virulent strains in the field over time, MDV remains a serious threat to the poultry industry. More than 40 yr after MDV identification as a herpesvirus, the visualization and purification of fully enveloped infectious particles remain a challenge for biologists. The various strategies used to detect such hidden particles by electron microscopy are reviewed herein. It is now generally accepted that the production of cell-free virions only occurs in the feather follicle epithelium and is associated with viral, cellular, or both molecular determinants expressed in this tissue. This tissue is considered the only source of efficient virus shedding into the environment and therefore the origin of successful transmission in birds. In other avian tissues or permissive cell cultures, MDV replication only leads to a very low number of intracellular enveloped virions. In the absence of detectable extracellular enveloped virions in cell culture, the nature of the transmitted infectious material and its mechanisms of spread from cell to cell remain to be deciphered. An attempt is made to bring together the current knowledge on MDV morphogenesis and spread, and new approaches that could help understand MDV morphogenesis are discussed. PMID:23901745

  3. Tribolium embryo morphogenesis

    PubMed Central

    Benton, Matthew A; Pavlopoulos, Anastasios

    2014-01-01

    Development of multicellular organisms depends on patterning and growth mechanisms encoded in the genome, but also on the physical properties and mechanical interactions of the constituent cells that interpret these genetic cues. This fundamental biological problem requires integrated studies at multiple levels of biological organization: from genes, to cell behaviors, to tissue morphogenesis. We have recently combined functional genetics with live imaging approaches in embryos of the insect Tribolium castaneum, in order to understand their remarkable transformation from a uniform single-layered blastoderm into a condensed multi-layered embryo covered by extensive extra-embryonic tissues. We first developed a quick and reliable methodology to fluorescently label various cell components in entire Tribolium embryos. Live imaging of labeled embryos at single cell resolution provided detailed descriptions of cell behaviors and tissue movements during normal embryogenesis. We then compared cell and tissue dynamics between wild-type and genetically perturbed embryos that exhibited altered relative proportions of constituent tissues. This systematic comparison led to a qualitative model of the molecular, cellular and tissue interactions that orchestrate the observed epithelial rearrangements. We expect this work to establish the Tribolium embryo as a powerful and attractive model system for biologists and biophysicists interested in the molecular, cellular and mechanical control of tissue morphogenesis. PMID:24451992

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

    PubMed Central

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

    2009-01-01

    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 multi-cellular 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Genetics, chance, and morphogenesis.

    PubMed Central

    Kurnit, D M; Layton, W M; Matthysse, S

    1987-01-01

    We posit that chance plays a major role in the occurrence of many common malformations that cluster in families but recur less frequently than expected for simple Mendelian traits. Once the role of random effects is accepted, the segregation of such malformations may be explained on the basis of Mendelian transmission of a single abnormal gene that predisposes to, but does not always result in, the abnormal phenotype. We apply a stochastic (probabilistic) single-gene model to the occurrence of malformations in mouse and man. The stochastic single-gene model suggests the feasibility of isolating individual genes that determine morphogenesis and sets limits on the precision with which the recurrence of malformations can be predicted. Images p[984]-a Fig. 6 PMID:3687945

  10. Molecular signaling in feather morphogenesis.

    PubMed

    Lin, Chih-Min; Jiang, Ting Xin; Widelitz, Randall B; Chuong, Cheng-Ming

    2006-12-01

    The development and regeneration of feathers have gained much attention recently because of progress in the following areas. First, pattern formation. The exquisite spatial arrangement provides a simple model for decoding the rules of morphogenesis. Second, stem cell biology. In every molting, a few stem cells have to rebuild the entire epithelial organ, providing much to learn on how to regenerate an organ physiologically. Third, evolution and development ('Evo-Devo'). The discovery of feathered dinosaur fossils in China prompted enthusiastic inquiries about the origin and evolution of feathers. Progress has been made in elucidating feather morphogenesis in five successive phases: macro-patterning, micro-patterning, intra-bud morphogenesis, follicle morphogenesis and regenerative cycling. PMID:17049829

  11. Molecular signaling in feather morphogenesis

    PubMed Central

    Lin, Chih-Min; Jiang, Ting Xin; Widelitz, Randall B; Chuong, Cheng-Ming

    2015-01-01

    The development and regeneration of feathers have gained much attention recently because of progress in the following areas. First, pattern formation. The exquisite spatial arrangement provides a simple model for decoding the rules of morphogenesis. Second, stem cell biology. In every molting, a few stem cells have to rebuild the entire epithelial organ, providing much to learn on how to regenerate an organ physiologically. Third, evolution and development (‘Evo-Devo’). The discovery of feathered dinosaur fossils in China prompted enthusiastic inquiries about the origin and evolution of feathers. Progress has been made in elucidating feather morphogenesis in five successive phases: macro-patterning, micro-patterning, intra-bud morphogenesis, follicle morphogenesis and regenerative cycling. PMID:17049829

  12. 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

  13. Vertebrate Reproduction.

    PubMed

    Kornbluth, Sally; Fissore, Rafael

    2015-10-01

    Vertebrate reproduction requires a myriad of precisely orchestrated events-in particular, the maternal production of oocytes, the paternal production of sperm, successful fertilization, and initiation of early embryonic cell divisions. These processes are governed by a host of signaling pathways. Protein kinase and phosphatase signaling pathways involving Mos, CDK1, RSK, and PP2A regulate meiosis during maturation of the oocyte. Steroid signals-specifically testosterone-regulate spermatogenesis, as does signaling by G-protein-coupled hormone receptors. Finally, calcium signaling is essential for both sperm motility and fertilization. Altogether, this signaling symphony ensures the production of viable offspring, offering a chance of genetic immortality. PMID:26430215

  14. 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

  15. SnapShot: Branching Morphogenesis.

    PubMed

    Chuong, Cheng-Ming; Bhat, Ramray; Widelitz, Randall B; Bissell, Mina J

    2014-08-28

    Ectodermal appendages such as feathers, hair, mammary glands, salivary glands, and sweat glands form branches, allowing much-increased surface for functional differentiation and secretion. Here, the principles of branching morphogenesis are exemplified by the mammary gland and feathers. PMID:25171418

  16. Cellular Mechanisms of Drosophila Heart Morphogenesis

    PubMed Central

    Vogler, Georg; Bodmer, Rolf

    2015-01-01

    Many of the major discoveries in the fields of genetics and developmental biology have been made using the fruit fly, Drosophila melanogaster. With regard to heart development, the conserved network of core cardiac transcription factors that underlies cardiogenesis has been studied in great detail in the fly, and the importance of several signaling pathways that regulate heart morphogenesis, such as Slit/Robo, was first shown in the fly model. Recent technological advances have led to a large increase in the genomic data available from patients with congenital heart disease (CHD). This has highlighted a number of candidate genes and gene networks that are potentially involved in CHD. To validate genes and genetic interactions among candidate CHD-causing alleles and to better understand heart formation in general are major tasks. The specific limitations of the various cardiac model systems currently employed (mammalian and fish models) provide a niche for the fly model, despite its evolutionary distance to vertebrates and humans. Here, we review recent advances made using the Drosophila embryo that identify factors relevant for heart formation. These underline how this model organism still is invaluable for a better understanding of CHD. PMID:26236710

  17. Centrosome positioning in vertebrate development

    PubMed Central

    Tang, Nan; Marshall, Wallace F.

    2012-01-01

    Summary The centrosome, a major organizer of microtubules, has important functions in regulating cell shape, polarity, cilia formation and intracellular transport as well as the position of cellular structures, including the mitotic spindle. By means of these activities, centrosomes have important roles during animal development by regulating polarized cell behaviors, such as cell migration or neurite outgrowth, as well as mitotic spindle orientation. In recent years, the pace of discovery regarding the structure and composition of centrosomes has continuously accelerated. At the same time, functional studies have revealed the importance of centrosomes in controlling both morphogenesis and cell fate decision during tissue and organ development. Here, we review examples of centrosome and centriole positioning with a particular emphasis on vertebrate developmental systems, and discuss the roles of centrosome positioning, the cues that determine positioning and the mechanisms by which centrosomes respond to these cues. The studies reviewed here suggest that centrosome functions extend to the development of tissues and organs in vertebrates. PMID:23277534

  18. Regulation of tissue morphogenesis by endothelial cell-derived signals

    PubMed Central

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Adams, Ralf H.

    2016-01-01

    Summary Endothelial cells form an extensive network of blood vessels that has numerous essential functions in the vertebrate body. In addition to their well-established role as a versatile transport network, blood vessels can induce organ formation or direct growth and differentiation processes by providing signals in a paracrine (angiocrine) fashion. Tissue repair also requires the local restoration of vasculature. Endothelial cells are emerging as important signaling centers that coordinate regeneration and help to prevent deregulated, disease-promoting processes. Vascular cells are also part of stem cell niches and play key roles in hematopoiesis, bone formation and neurogenesis. Here, we will review these newly identified roles of endothelial cells in the regulation of organ morphogenesis, maintenance and regeneration. PMID:25529933

  19. Validation of three tools for identifying painful new osteoporotic vertebral fractures in older Chinese men: bone mineral density, Osteoporosis Self-Assessment Tool for Asians, and fracture risk assessment tool

    PubMed Central

    Lin, JiSheng; Yang, Yong; Fei, Qi; Zhang, XiaoDong; Ma, Zhao; Wang, Qi; Li, JinJun; Li, Dong; Meng, Qian; Wang, BingQiang

    2016-01-01

    Objective This cross-sectional study compared three tools for predicting painful new osteoporotic vertebral fractures (PNOVFs) in older Chinese men: bone mineral density (BMD), the Osteoporosis Self-Assessment Tool for Asians (OSTA), and the World Health Organization fracture risk assessment tool (FRAX) (without BMD). Methods Men aged ≥50 years were apportioned to a group for men with fractures who had undergone percutaneous vertebroplasty (n=111), or a control group of healthy men (n=385). Fractures were verified on X-ray and magnetic resonance imaging. BMD T-scores were determined by dual energy X-ray absorptiometry. Diagnosis of osteoporosis was determined by a BMD T-score of ≤2.5 standard deviations below the average for a young adult at peak bone density at the femoral neck, total hip, or L1–L4. Demographic and clinical risk factor data were self-reported through a questionnaire. BMD, OSTA, and FRAX scores were assessed for identifying PNOVFs via receiver-operating characteristic (ROC) curves. Optimal cutoff points, sensitivity, specificity, and areas under the ROC curves (AUCs) were determined. Results Between the men with fractures and the control group, there were significant differences in BMD T-scores (at femoral neck, total hip, and L1–L4), and OSTA and FRAX scores. In those with fractures, only 53.15% satisfied the criteria for osteoporosis. Compared to BMD or OSTA, the FRAX score had the best predictive value for PNOVFs: the AUC of the FRAX score (cutoff =2.9%) was 0.738, and the sensitivity and specificity were 82% and 62%, respectively. Conclusion FRAX may be a valuable tool for identifying PNOVFs in older Chinese men. PMID:27217730

  20. Dentition development and budding morphogenesis.

    PubMed

    Peterková, R; Peterka, M; Viriot, L; Lesot, H

    2000-01-01

    The development of functional teeth in the mouse has been widely used as a model to study general mechanisms of organogenesis. Compared with other mammals, in which three incisors, one canine, four premolars, and three molars may occur even in each dental quadrant, the mouse functional dentition is strongly reduced. It comprises only one incisor separated from three molars by a toothless gap diastema at the location of the missing teeth. However, mouse embryos also develop transient vestigial dental primordia between the incisor and molar germs in both the upper and lower jaws. These rudimental structures regress, and epithelial apoptosis is involved in this process. The existence of the vestigial dental structures allowed a better assessment of the periodicity in the mouse dentition, which extends opportunities for the interpretation of molecular data on tooth development. We compared the dentition development with tentative models of budding morphogenesis in other epithelial appendages lungs and feathers. We suggested how developmental control by signaling molecules, including bone morphogenetic protein (Bmp), sonic hedgehog (Shh), and fibroblast growth factor (Fgf), can be similarly involved during budding morphogenesis of dentition and other epithelial appendages. We propose that epithelial apoptosis plays an important role in achieving specific features of dentition, whose development involves both budding and its more complex variant branching. The failure of segregation of the originating buds supports the participation of the concrescence of several tooth primordia in the evolutionary differentiation of mammalian teeth. PMID:11354512

  1. Nanopatterned protein microrings from a diatom that direct silica morphogenesis.

    PubMed

    Scheffel, André; Poulsen, Nicole; Shian, Samuel; Kröger, Nils

    2011-02-22

    Diatoms are eukaryotic microalgae that produce species-specifically structured cell walls made of SiO(2) (silica). Formation of the intricate silica structures of diatoms is regarded as a paradigm for biomolecule-controlled self-assembly of three-dimensional, nano- to microscale-patterned inorganic materials. Silica formation involves long-chain polyamines and phosphoproteins (silaffins and silacidins), which are readily soluble in water, and spontaneously form dynamic supramolecular assemblies that accelerate silica deposition and influence silica morphogenesis in vitro. However, synthesis of diatom-like silica structure in vitro has not yet been accomplished, indicating that additional components are required. Here we describe the discovery and intracellular location of six novel proteins (cingulins) that are integral components of a silica-forming organic matrix (microrings) in the diatom Thalassiosira pseudonana. The cingulin-containing microrings are specifically associated with girdle bands, which constitute a substantial part of diatom biosilica. Remarkably, the microrings exhibit protein-based nanopatterns that closely resemble characteristic features of the girdle band silica nanopatterns. Upon the addition of silicic acid the microrings become rapidly mineralized in vitro generating nanopatterned silica replicas of the microring structures. A silica-forming organic matrix with characteristic nanopatterns was also discovered in the diatom Coscinodiscus wailesii, which suggests that preassembled protein-based templates might be general components of the cellular machinery for silica morphogenesis in diatoms. These data provide fundamentally new insight into the molecular mechanisms of biological silica morphogenesis, and may lead to the development of self-assembled 3D mineral forming protein scaffolds with designed nanopatterns for a host of applications in nanotechnology. PMID:21300899

  2. 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

  3. 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

  4. Microtubule dynamics in neuronal morphogenesis.

    PubMed

    Sakakibara, Akira; Ando, Ryota; Sapir, Tamar; Tanaka, Teruyuki

    2013-07-01

    Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytoskeleton provides physical support to shape the fine structure of neuronal processes. MT-based motors play important roles in nucleokinesis, process formation and retraction. Regulation of MT stability downstream of extracellular cues is proposed to be critical for axonogenesis. Axons and dendrites exhibit different patterns of MT organization, underlying the divergent functions of these processes. Centrosomal positioning has drawn the attention of researchers because it is a major clue to understanding neuronal MT organization. In this review, we focus on how recent advances in live imaging have revealed the dynamics of MT organization and centrosome positioning during neural development. PMID:23864552

  5. Microtubule dynamics in neuronal morphogenesis

    PubMed Central

    Sakakibara, Akira; Ando, Ryota; Sapir, Tamar; Tanaka, Teruyuki

    2013-01-01

    Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytoskeleton provides physical support to shape the fine structure of neuronal processes. MT-based motors play important roles in nucleokinesis, process formation and retraction. Regulation of MT stability downstream of extracellular cues is proposed to be critical for axonogenesis. Axons and dendrites exhibit different patterns of MT organization, underlying the divergent functions of these processes. Centrosomal positioning has drawn the attention of researchers because it is a major clue to understanding neuronal MT organization. In this review, we focus on how recent advances in live imaging have revealed the dynamics of MT organization and centrosome positioning during neural development. PMID:23864552

  6. 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

  7. 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. PMID:26177834

  8. 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

  9. 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…

  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. PMID:26608609

  11. Gene expression throughout a vertebrate's embryogenesis

    PubMed Central

    2011-01-01

    Background Describing the patterns of gene expression during embryonic development has broadened our understanding of the processes and patterns that define morphogenesis. Yet gene expression patterns have not been described throughout vertebrate embryogenesis. This study presents statistical analyses of gene expression during all 40 developmental stages in the teleost Fundulus heteroclitus using four biological replicates per stage. Results Patterns of gene expression for 7,000 genes appear to be important as they recapitulate developmental timing. Among the 45% of genes with significant expression differences between pairs of temporally adjacent stages, significant differences in gene expression vary from as few as five to more than 660. Five adjacent stages have disproportionately more significant changes in gene expression (> 200 genes) relative to other stages: four to eight and eight to sixteen cell stages, onset of circulation, pre and post-hatch, and during complete yolk absorption. The fewest differences among adjacent stages occur during gastrulation. Yet, at stage 16, (pre-mid-gastrulation) the largest number of genes has peak expression. This stage has an over representation of genes in oxidative respiration and protein expression (ribosomes, translational genes and proteases). Unexpectedly, among all ribosomal genes, both strong positive and negative correlations occur. Similar correlated patterns of expression occur among all significant genes. Conclusions These data provide statistical support for the temporal dynamics of developmental gene expression during all stages of vertebrate development. PMID:21356103

  12. 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

  13. 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

  14. 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

  15. 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

  16. Extreme morphogenesis in the central caucasus mountains

    NASA Astrophysics Data System (ADS)

    Bulanov, S. A.; Karavaev, V. A.; Seminozhenko, S. S.

    2016-05-01

    The results of field observations on exogenic morphogenesis in the upper reaches of the Cherek Balkarskii River (Kabardino-Balkaria) are presented. It is established that different components of the extreme morphogenetic process confined to the distribution area of unconsolidated Quaternary sediments are closely interrelated to form a peculiar geomorphological mechanism.

  17. 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

  18. Split top: a maternal cathepsin B that regulates dorsoventral patterning and morphogenesis.

    PubMed

    Langdon, Yvette G; Fuentes, Ricardo; Zhang, Hong; Abrams, Elliott W; Marlow, Florence L; Mullins, Mary C

    2016-03-15

    The vertebrate embryonic dorsoventral axis is established and patterned by Wnt and bone morphogenetic protein (BMP) signaling pathways, respectively. Whereas Wnt signaling establishes the dorsal side of the embryo and induces the dorsal organizer, a BMP signaling gradient patterns tissues along the dorsoventral axis. Early Wnt signaling is provided maternally, whereas BMP ligand expression in the zebrafish is zygotic, but regulated by maternal factors. Concomitant with BMP activity patterning dorsoventral axial tissues, the embryo also undergoes dramatic morphogenetic processes, including the cell movements of gastrulation, epiboly and dorsal convergence. Although the zygotic regulation of these cell migration processes is increasingly understood, far less is known of the maternal regulators of these processes. Similarly, the maternal regulation of dorsoventral patterning, and in particular the maternal control of ventral tissue specification, is poorly understood. We identified split top, a recessive maternal-effect zebrafish mutant that disrupts embryonic patterning upstream of endogenous BMP signaling. Embryos from split top mutant females exhibit a dorsalized embryonic axis, which can be rescued by BMP misexpression or by derepressing endogenous BMP signaling. In addition to dorsoventral patterning defects, split top mutants display morphogenesis defects that are both BMP dependent and independent. These morphogenesis defects include incomplete dorsal convergence, delayed epiboly progression and an early lysis phenotype during gastrula stages. The latter two morphogenesis defects are associated with disruption of the actin and microtubule cytoskeleton within the yolk cell and defects in the outer enveloping cell layer, which are both known mediators of epiboly movements. Through chromosomal mapping and RNA sequencing analysis, we identified the lysosomal endopeptidase cathepsin Ba (ctsba) as the gene deficient in split top embryos. Our results identify a novel

  19. A review of anatomical and mechanical factors affecting vertebral body integrity

    PubMed Central

    2004-01-01

    Background: The aetiology of osteoporotic vertebral fracture is multifactorial and may be conceptualised using a systems framework. Previous studies have established several correlates of vertebral fracture including reduced vertebral cross-sectional area, weakness in back extensor muscles, reduced bone mineral density, increasing age, worsening kyphosis and recent vertebral fracture. Alterations in these physical characteristics may influence biomechanical loads and neuromuscular control of the trunk and contribute to changes in subregional bone mineral density of the vertebral bodies. Methods: This review discusses factors that have received less attention in the literature, which may contribute to the development of vertebral fracture. A literature review was conducted using electronic databases including Medline, Cinahl and ISI Web of Science to examine the potential contribution of trabecular architecture, subregional bone mineral density, vertebral geometry, muscle force, muscle strength, neuromuscular control and intervertebral disc integrity to the aetiology of osteoporotic vertebral fracture. Interpretation: A better understanding of factors such as biomechanical loading and neuromuscular control of the trunk may help to explain the high incidence of subsequent vertebral fracture after sustaining an initial vertebral fracture. Consideration of these issues may be important in the development of prevention and management strategies. PMID:15912196

  20. Kinship affects morphogenesis in cannibalistic salamanders.

    PubMed

    Pfennig, D W; Collins, J P

    1993-04-29

    Inclusive fitness theory predicts that organisms can often increase their fitness by helping relatives. Indeed, many animals modify their behaviour towards kin in a fashion consistent with theory. Morphogenesis may also be sensitive to kinship environment, especially in species that facultatively produce distinct morphs that differ in their ability to harm relatives, such as those that produce alternative cannibalistic and non-cannibalistic phenotypes. We tested this hypothesis by examining whether consanguinity affected the probability that structurally distinctive cannibal morphs would develop in larval Arizona tiger salamanders (Ambystoma tigrinum nebulosum). We report here that when tiger salamander larvae are reared in mixed-brood groups they are significantly more likely to develop the cannibal morphology and at an earlier age than siblings reared in pure-sibship groups. In general, morphogenesis may be responsive to kinship in any species that facultatively develops structures that can be used against conspecifics as weaponry. PMID:8479520

  1. 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

  2. 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

  3. 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

  4. Clinical Management of Vertebral Compression Fractures.

    PubMed

    Miller, Paul D

    2016-01-01

    Vertebral compression fractures (VCF's) are the most common form of osteoporotic fractures. Whether symptomatic or asymptomatic, they both represent a high risk for not only vertebral but also nonvertebral fractures in untreated populations. This high risk of future fracture after a VCF is independent of the T-score because bone strength is a combination of bone mineral density and bone quality. VCFs are the single greatest risk for future fractures at all other skeletal sites in untreated populations, including hip fractures. They are often unrecognized despite their exceptionally high prevalence in all genders and most ethnic groups as age increases. This article highlights some of the key messages about VCF's, and how assessment for their presence and then management will reduce the risk of all osteoporotic fractures. PMID:26439186

  5. 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

  6. Mathematical modeling of vertebrate limb development.

    PubMed

    Zhang, Yong-Tao; Alber, Mark S; Newman, Stuart A

    2013-05-01

    In this paper, we review the major mathematical and computational models of vertebrate limb development and their roles in accounting for different aspects of this process. The main aspects of limb development that have been modeled include outgrowth and shaping of the limb bud, establishment of molecular gradients within the bud, and formation of the skeleton. These processes occur interdependently during development, although (as described in this review), there are various interpretations of the biological relationships among them. A wide range of mathematical and computational methods have been used to study these processes, including ordinary and partial differential equation systems, cellular automata and discrete, stochastic models, finite difference methods, finite element methods, the immersed boundary method, and various combinations of the above. Multiscale mathematical modeling and associated computational simulation have become integrated into the study of limb morphogenesis and pattern formation to an extent with few parallels in the field of developmental biology. These methods have contributed to the design and analysis of experiments employing microsurgical and genetic manipulations, evaluation of hypotheses for limb bud outgrowth, interpretation of the effects of natural mutations, and the formulation of scenarios for the origination and evolution of the limb skeleton. PMID:23219575

  7. 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.

  8. Airway branching morphogenesis in three dimensional culture

    PubMed Central

    2010-01-01

    Background Lungs develop from the fetal digestive tract where epithelium invades the vascular rich stroma in a process called branching morphogenesis. In organogenesis, endothelial cells have been shown to be important for morphogenesis and the maintenance of organ structure. The aim of this study was to recapitulate human lung morphogenesis in vitro by establishing a three dimensional (3D) co-culture model where lung epithelial cells were cultured in endothelial-rich stroma. Methods We used a human bronchial epithelial cell line (VA10) recently developed in our laboratory. This cell line cell line maintains a predominant basal cell phenotype, expressing p63 and other basal markers such as cytokeratin-5 and -14. Here, we cultured VA10 with human umbilical vein endothelial cells (HUVECs), to mimic the close interaction between these cell types during lung development. Morphogenesis and differentiation was monitored by phase contrast microscopy, immunostainings and confocal imaging. Results We found that in co-culture with endothelial cells, the VA10 cells generated bronchioalveolar like structures, suggesting that lung epithelial branching is facilitated by the presence of endothelial cells. The VA10 derived epithelial structures display various complex patterns of branching and show partial alveolar type-II differentiation with pro-Surfactant-C expression. The epithelial origin of the branching VA10 colonies was confirmed by immunostaining. These bronchioalveolar-like structures were polarized with respect to integrin expression at the cell-matrix interface. The endothelial-induced branching was mediated by soluble factors. Furthermore, fibroblast growth factor receptor-2 (FGFR-2) and sprouty-2 were expressed at the growing tips of the branching structures and the branching was inhibited by the FGFR-small molecule inhibitor SU5402. Discussion In this study we show that a human lung epithelial cell line can be induced by endothelial cells to form branching

  9. 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

  10. [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

  11. 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

  12. Retinoic acid differentially affects in vitro proliferation, differentiation and mineralization of two fish bone-derived cell lines: different gene expression of nuclear receptors and ECM proteins.

    PubMed

    Fernández, Ignacio; Tiago, Daniel M; Laizé, Vincent; Leonor Cancela, M; Gisbert, Enric

    2014-03-01

    Retinoic acid (RA), the main active metabolite of vitamin A, regulates vertebrate morphogenesis through signaling pathways not yet fully understood. Such process involves the specific activation of retinoic acid and retinoid X receptors (RARs and RXRs), which are nuclear receptors of the steroid/thyroid hormone receptor superfamily. Teleost fish are suitable models to study vertebrate development, such as skeletogenesis. Cell systems capable of in vitro mineralization have been developed for several fish species and may provide new insights into the specific cellular and molecular events related to vitamin A activity in bone, complementary to in vivo studies. This work aims at investigating the in vitro effects of RA (0.5 and 12.5 μM) on proliferation, differentiation and extracellular matrix (ECM) mineralization of two gilthead seabream bone-derived cell lines (VSa13 and VSa16), and at identifying molecular targets of its action through gene expression analysis. RA induced phenotypic changes and cellular proliferation was inhibited in both cell lines in a cell type-dependent manner (36-59% in VSa13 and 17-46% in VSa16 cells). While RA stimulated mineral deposition in VSa13 cell cultures (50-62% stimulation), it inhibited the mineralization of extracellular matrix in VSa16 cells (11-57% inhibition). Expression of hormone receptor genes (rars and rxrs), and extracellular matrix-related genes such as matrix and bone Gla proteins (mgp and bglap), osteopontin (spp1) and type I collagen (col1a1) were differentially regulated upon exposure to RA in proliferating, differentiating and mineralizing cultures of VSa13 and VSa16 cells. Altogether, our results show: (i) RA affects proliferative and mineralogenic activities in two fish skeletal cell types and (ii) that during phenotype transitions, specific RA nuclear receptors and bone-related genes are differentially expressed in a cell type-dependent manner. PMID:24291400

  13. Development and evolution of the vertebrate primary mouth.

    PubMed

    Soukup, Vladimír; Horácek, Ivan; Cerny, Robert

    2013-01-01

    The vertebrate oral region represents a key interface between outer and inner environments, and its structural and functional design is among the limiting factors for survival of its owners. Both formation of the respective oral opening (primary mouth) and establishment of the food-processing apparatus (secondary mouth) require interplay between several embryonic tissues and complex embryonic rearrangements. Although many aspects of the secondary mouth formation, including development of the jaws, teeth or taste buds, are known in considerable detail, general knowledge about primary mouth formation is regrettably low. In this paper, primary mouth formation is reviewed from a comparative point of view in order to reveal its underestimated morphogenetic diversity among, and also within, particular vertebrate clades. In general, three main developmental modes were identified. The most common is characterized by primary mouth formation via a deeply invaginated ectodermal stomodeum and subsequent rupture of the bilaminar oral membrane. However, in salamander, lungfish and also in some frog species, the mouth develops alternatively via stomodeal collar formation contributed both by the ecto- and endoderm. In ray-finned fishes, on the other hand, the mouth forms via an ectoderm wedge and later horizontal detachment of the initially compressed oral epithelia with probably a mixed germ-layer derivation. A very intriguing situation can be seen in agnathan fishes: whereas lampreys develop their primary mouth in a manner similar to the most common gnathostome pattern, hagfishes seem to undergo a unique oropharyngeal morphogenesis when compared with other vertebrates. In discussing the early formative embryonic correlates of primary mouth formation likely to be responsible for evolutionary-developmental modifications of this area, we stress an essential role of four factors: first, positioning and amount of yolk tissue; closely related to, second, endoderm formation during

  14. 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

  15. Comparative analysis of neural crest cell death, migration, and function during vertebrate embryogenesis.

    PubMed

    Kulesa, Paul; Ellies, Debra L; Trainor, Paul A

    2004-01-01

    Cranial neural crest cells are a multipotent, migratory population that generates most of the cartilage, bone, connective tissue and peripheral nervous system in the vertebrate head. Proper neural crest cell patterning is essential for normal craniofacial morphogenesis and is highly conserved among vertebrates. Neural crest cell patterning is intimately connected to the early segmentation of the neural tube, such that neural crest cells migrate in discrete segregated streams. Recent advances in live embryo imaging have begun to reveal the complex behaviour of neural crest cells which involve intricate cell-cell and cell-environment interactions. Despite the overall similarity in neural crest cell migration between distinct vertebrates species there are important mechanistic differences. Apoptosis for example, is important for neural crest cell patterning in chick embryos but not in mouse, frog or fish embryos. In this paper we highlight the potential evolutionary significance of such interspecies differences in jaw development and evolution. Developmental Dynamics 229:14-29, 2004. PMID:14699574

  16. Intrinsic and extrinsic mechanisms of dendritic morphogenesis.

    PubMed

    Dong, Xintong; Shen, Kang; Bülow, Hannes E

    2015-01-01

    The complex, branched morphology of dendrites is a cardinal feature of neurons and has been used as a criterion for cell type identification since the beginning of neurobiology. Regulated dendritic outgrowth and branching during development form the basis of receptive fields for neurons and are essential for the wiring of the nervous system. The cellular and molecular mechanisms of dendritic morphogenesis have been an intensely studied area. In this review, we summarize the major experimental systems that have contributed to our understandings of dendritic development as well as the intrinsic and extrinsic mechanisms that instruct the neurons to form cell type-specific dendritic arbors. PMID:25386991

  17. 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

  18. 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

  19. 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

  20. Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesis.

    PubMed

    Gago-Rodrigues, Ines; Fernández-Miñán, Ana; Letelier, Joaquin; Naranjo, Silvia; Tena, Juan J; Gómez-Skarmeta, José L; Martinez-Morales, Juan R

    2015-01-01

    The self-organized morphogenesis of the vertebrate optic cup entails coupling the activation of the retinal gene regulatory network to the constriction-driven infolding of the retinal epithelium. Yet the genetic mechanisms underlying this coordination remain largely unexplored. Through phylogenetic footprinting and transgenesis in zebrafish, here we examine the cis-regulatory landscape of opo, an endocytosis regulator essential for eye morphogenesis. Among the different conserved enhancers identified, we isolate a single retina-specific element (H6_10137) and show that its activity depends on binding sites for the retinal determinant Vsx2. Gain- and loss-of-function experiments and ChIP analyses reveal that Vsx2 regulates opo expression through direct binding to this retinal enhancer. Furthermore, we show that vsx2 knockdown impairs the primary optic cup folding. These data support a model by which vsx2, operating through the effector gene opo, acts as a central transcriptional node that coordinates neural retina patterning and optic cup invagination in zebrafish. PMID:25963169

  1. The role of Sdf-1α signaling in Xenopus laevis somite morphogenesis

    PubMed Central

    Leal, Marisa A.; Fickel, Sarah R.; Sabillo, Armbien; Ramirez, Julio; Vergara, Hernando Martínez; Nave, Ceazar; Saw, Daniel; Domingo, Carmen R.

    2014-01-01

    Background Stromal derived factor-1α (sdf-1α), a chemoattractant chemokine, plays a major role in tumor growth, angiogenesis, metastasis and in embryogenesis. The sdf-1α signaling pathway has also been shown to be important for somite rotation in zebrafish (Hollway, et al 2007). Given the known similarities and differences between zebrafish and Xenopus laevis somitogenesis, we sought to determine whether the role of sdf-1α is conserved in Xenopus laevis. Results Using a morpholino approach, we demonstrate that knockdown of sdf-1α or its receptor, cxcr4, leads to a significant disruption in somite rotation and myotome alignment. We further show that depletion of sdf-1α or cxcr4 leads to the near absence of β-dystroglycan and laminin expression at the intersomitic boundaries. Finally, knockdown of sdf-1α decreases the level of activated RhoA, a small GTPase known to regulate cell shape and movement. Conclusion Our results show that sdf-1α signaling regulates somite cell migration, rotation and myotome alignment by directly or indirectly regulating dystroglycan expression and RhoA activation. These findings support the conservation of sdf-1α signaling in vertebrate somite morphogenesis; however, the precise mechanism by which this signaling pathway influences somite morphogenesis is different between the fish and the frog. PMID:24357195

  2. 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

  3. 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

  4. 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

  5. Semaphorin controls epidermal morphogenesis by stimulating mRNA translation via eIF2α in Caenorhabditis elegans

    PubMed Central

    Nukazuka, Akira; Fujisawa, Hajime; Inada, Toshifumi; Oda, Yoichi; Takagi, Shin

    2008-01-01

    Conserved semaphorin–plexin signaling systems govern various aspects of animal development, including axonal guidance in vertebrates and epidermal morphogenesis in Caenorhabditis elegans. Here we provide in vivo evidence that stimulation of mRNA translation via eukaryotic initiation factor 2α (eIF2α) is an essential downstream event of semaphorin signaling in C. elegans. In semaphorin/plexin mutants, a marked elevation in the phosphorylation of eIF2α is observed, which causes translation repression and is causally related to the morphological epidermal phenotype in the mutants. Conversely, removal of constraints on translation by genetically reducing the eIF2α phosphorylation largely bypasses requirement for the semaphorin signal in epidermal morphogenesis. We also identify an actin-depolymerizing factor/cofilin, whose expression in the mutants is predominantly repressed, as a major translational target of semaphorin signaling. Thus, our results reveal a physiological significance for translation of mRNAs for cytoskeletal regulators, linking environmental cues to cytoskeletal rearrangement during cellular morphogenesis in vivo. PMID:18413715

  6. Vertebral Angiosarcoma. Case Study.

    PubMed

    Guzik, Grzegorz

    2015-01-01

    Bone angiosarcomas, especially vertebral angiosarcomas, are very rare. There are no studies based on large clinical samples in the literature, and only a few single case reports can be found. The symptoms of the disease are not specific. It is usually detected incidentally or at a late stage when pathological vertebral fractures or neurological complications occur. Diagnostic imaging and history help to recognize the tumour behind the symptoms, but do not allow accurate clinical diagnosis. The basis for a diagnosis is the histopathological examination supported by immunohistochemistry (IHC) assays. The case of a 26-year-old woman with an angiosarcoma involving the eighth thoracic vertebra we report reflects diagnostic problems adversely affecting the efficacy and accuracy of treatment offered to patients. The patient underwent three surgeries of the spine, including two biopsies. A needle biopsy did not provide sufficient information for the diagnosis. An open excisional biopsy, which at the same time temporarily reduced neurological deficits in the patient, was the only chance to obtain an accurate diagnosis. The third surgery was posterior decompression of the spinal cord due to the rapidly escalating paraparesis. It was not until 8 weeks later that the final diagnosis was established. At that time, the patient could not be qualified for any supplementary treatment. The patient died in hospital 6 months after the onset of disease. PMID:26468177

  7. Peripheral nerve morphogenesis induced by scaffold micropatterning.

    PubMed

    Cerri, Federica; Salvatore, Luca; Memon, Danish; Martinelli Boneschi, Filippo; 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

    2014-04-01

    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 micro-structure 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 micro-structure 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

  8. The epidemiology of vertebral fractures. European Vertebral Osteoporosis Study Group.

    PubMed

    Cooper, C; O'Neill, T; Silman, A

    1993-01-01

    Vertebral fractures are recognised as a hallmark of osteoporosis, yet little is known of their epidemiology. This deficiency limits accurate characterisation of the public health importance of osteoporosis. Assessment of the impact of vertebral fractures has been hampered by the absence of formal criteria for identifying fractures on a thoracolumbar radiograph. Initial methods relying upon subjective radiological assessments have given way to morphometric measurements of vertebral heights, with deformities defined according to various algorithms. These methods have been used in a series of studies performed in Rochester, MN, to determine the incidence, outcome, and time trends of vertebral deformities. The results suggest a prevalence rate of vertebral deformity of 25.3 per 100 Rochester women aged 50 years and over (95% CI, 22.3-28.2), with an estimated incidence of 17.8 per 1,000 person-years. The incidence of clinically diagnosed vertebral fractures among women in the same population was 5.3 per 1,000 person-years, suggesting that around 30% of such deformities in women receive clinical attention. Morphometric measurement on the radiographs of women with clinically diagnosed fractures revealed that 80% had grade 2 ( > 4 SD) deformities. Comparable data on the occurrence and health impact of vertebral deformities throughout Europe are urgently required. The European Vertebral Osteoporosis Study (EVOS) is a multicentre epidemiological study that aims to address this issue. It is designed as a radiographic prevalence study in 34 European centres.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8110529

  9. High Serum SHBG Predicts Incident Vertebral Fractures in Elderly Men

    PubMed Central

    Vandenput, Liesbeth; Mellström, Dan; Kindmark, Andreas; Johansson, Helena; Lorentzon, Mattias; Leung, Jason; Redlund‐Johnell, Inga; Rosengren, Björn E; Karlsson, Magnus K; Wang, Yi‐Xiang; Kwok, Timothy

    2016-01-01

    ABSTRACT Previous prospective cohort studies have shown that serum levels of sex steroids and sex hormone‐binding globulin (SHBG) associate with nonvertebral fracture risk in men. The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is, however, less studied. Elderly men (aged ≥65 years) from Sweden and Hong Kong participating in the Osteoporotic Fractures in Men (MrOS) study had baseline estradiol and testosterone analyzed by gas chromatography–mass spectrometry (GC‐MS) and SHBG by immunoradiometric assay (IRMA). Incident clinical vertebral fractures (n = 242 cases) were evaluated in 4324 men during an average follow‐up of 9.1 years. In a subsample of these men (n = 2256), spine X‐rays were obtained at baseline and after an average follow‐up of 4.3 years to identify incident radiographic vertebral fractures (n = 157 cases). The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models, respectively. Neither serum estradiol (hazard ratio [HR] per SD increase = 0.93, 95% confidence interval [CI] 0.80–1.08) nor testosterone (1.05, 0.91–1.21) predicted incident clinical vertebral fractures in age‐adjusted models in the combined data set. High serum SHBG, however, associated with increased clinical vertebral fracture risk (1.24, 1.12–1.37). This association remained significant after further adjustment for FRAX with or without bone mineral density (BMD). SHBG also associated with increased incident radiographic vertebral fracture risk (combined data set; odds ratio [OR] per SD increase = 1.23, 95% CI 1.05–1.44). This association remained significant after adjustment for FRAX with or without BMD. In conclusion, high SHBG predicts incident clinical and radiographic vertebral fractures in elderly men and adds moderate information beyond FRAX with BMD for vertebral fracture risk prediction. © 2015 The

  10. 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.

  11. 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

  12. 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...

  13. NUTRITIONAL CONTROL OF MORPHOGENESIS IN ARTHROBACTER CRYSTALLOPOIETES

    PubMed Central

    Ensign, Jerald C.; Wolfe, R. S.

    1964-01-01

    Ensign, Jerald C. (University of Illinois, Urbana), and R. S. Wolfe. Nutritional control of morphogenesis in Arthrobacter crystallopoietes. J. Bacteriol. 87:924–932. 1964.—Arthrobacter crystallopoietes exhibits the cyclic, morphological variation which is a characteristic of this genus. A simple chemically defined medium was developed in which this organism is restricted to growth and division entirely in the coccoid form. Addition singly to this medium of l-arginine, l-phenylalanine, l-asparagine, l-lysine, succinate, malate, fumarate, lactate, or butyrate results in the formation of the rod-shaped stage. A large number of other compounds either increase, have no effect on, or inhibit growth without inducing morphological change in the organisms. Images PMID:14137632

  14. 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.

  15. 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

  16. 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

  17. Early inductive events in ectodermal appendage morphogenesis.

    PubMed

    Biggs, Leah C; Mikkola, Marja L

    2014-01-01

    The embryonic surface ectoderm gives rise to the epidermis and ectodermal appendages including hair follicles, teeth, scales, feathers, and mammary, sweat, and salivary glands. Their early development proceeds largely the same through the induction, placode, and bud stages prior to diversification of epithelial morphogenesis which ultimately produces the wide array of mature organs. In this review we summarize the current knowledge on the molecular and cellular processes driving the shared stages of skin appendage development revealed by analysis of mouse mutants. We focus on three mammalian organs: hair follicle, tooth, and mammary gland. We reevaluate the information gained from classic epithelial-mesenchymal tissue recombination experiments in light of current molecular knowledge. We place special emphasis on the signaling pathways that mediate tissue interactions, and attempt to link the signaling outputs to changes in cellular behavior that ultimately shape the developing organ. PMID:24487243

  18. 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

  19. 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

  20. [Skin derivatives in ontogeny and phylogeny of vertebrates].

    PubMed

    Chernova, O F

    2009-01-01

    The skin of vertebrates has numerous and diverse derivatives, either located within the epithelial sheet itself (glands) or extending above its surface (teeth, scales, feathers, hairs, etc.). Many of them have a modular structure and constitute structural-functional units. Ontogenetically, all skin derivatives are of ectomesodermal origin, and their morphogenesis is subject to metabolic control, heterochronies (divergence in the timing of origination and development), and regulation by means of tissue interactions and molecular signaling via similar pathways. The diversification (origination of morphological diversity) of skin derivatives within the same morphological type is explained by the development of new generations of ectomesodermal structures separated be heterochronies and regulated by changes in the gradients of molecular signaling pathways under the influence of environmental factors. Evolutionary relationships between the majority of skin derivatives are obscure, except for teeth and glands associated with sensory organs, which evolved together with the latter. Apparently, many vertebrate skin derivatives (scales, feathers, hairs, and glands) originated as innovations at nodal stages of phylogeny and subsequently evolved convergently or in parallel. PMID:19391480

  1. Extracellular matrix and growth factors in branching morphogenesis

    NASA Technical Reports Server (NTRS)

    Hardman, P.; Spooner, B. S.

    1993-01-01

    The unifying hypothesis of the NSCORT in gravitational biology postulates that the ECM and growth factors are key interrelated components of a macromolecular regulatory system. The ECM is known to be important in growth and branching morphogenesis of embryonic organs. Growth factors have been detected in the developing embryo, and often the pattern of localization is associated with areas undergoing epithelial-mesenchymal interactions. Causal relationships between these components may be of fundamental importance in control of branching morphogenesis.

  2. 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

  3. Planar Cell Polarity Signaling in Collective Cell Movements During Morphogenesis and Disease

    PubMed Central

    Muñoz-Soriano, Verónica; Belacortu, Yaiza; Paricio, Nuria

    2012-01-01

    Collective and directed cell movements are crucial for diverse developmental processes in the animal kingdom, but they are also involved in wound repair and disease. During these processes groups of cells are oriented within the tissue plane, which is referred to as planar cell polarity (PCP). This requires a tight regulation that is in part conducted by the PCP pathway. Although this pathway was initially characterized in flies, subsequent studies in vertebrates revealed a set of conserved core factors but also effector molecules and signal modulators, which build the fundamental PCP machinery. The PCP pathway in Drosophila regulates several developmental processes involving collective cell movements such as border cell migration during oogenesis, ommatidial rotation during eye development, and embryonic dorsal closure. During vertebrate embryogenesis, PCP signaling also controls collective and directed cell movements including convergent extension during gastrulation, neural tube closure, neural crest cell migration, or heart morphogenesis. Similarly, PCP signaling is linked to processes such as wound repair, and cancer invasion and metastasis in adults. As a consequence, disruption of PCP signaling leads to pathological conditions. In this review, we will summarize recent findings about the role of PCP signaling in collective cell movements in flies and vertebrates. In addition, we will focus on how studies in Drosophila have been relevant to our understanding of the PCP molecular machinery and will describe several developmental defects and human disorders in which PCP signaling is compromised. Therefore, new discoveries about the contribution of this pathway to collective cell movements could provide new potential diagnostic and therapeutic targets for these disorders. PMID:23730201

  4. 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

  5. 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. PMID:11173834

  6. 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

  7. Epithelial dynamics of pancreatic branching morphogenesis

    PubMed Central

    Villasenor, Alethia; Chong, Diana C.; Henkemeyer, Mark; Cleaver, Ondine

    2010-01-01

    The mammalian pancreas is a highly branched gland, essential for both digestion and glucose homeostasis. Pancreatic branching, however, is poorly understood, both at the ultrastructural and cellular levels. In this article, we characterize the morphogenesis of pancreatic branches, from gross anatomy to the dynamics of their epithelial organization. We identify trends in pancreatic branch morphology and introduce a novel mechanism for branch formation, which involves transient epithelial stratification and partial loss of cell polarity, changes in cell shape and cell rearrangements, de novo tubulogenesis and epithelial tubule remodeling. In contrast to the classical epithelial budding and tube extension observed in other organs, a pancreatic branch takes shape as a multi-lumen tubular plexus coordinately extends and remodels into a ramifying, single-lumen ductal system. Moreover, our studies identify a role for EphB signaling in epithelial remodeling during pancreatic branching. Overall, these results illustrate distinct, step-wise cellular mechanisms by which pancreatic epithelium shapes itself to create a functional branching organ. PMID:21098570

  8. 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.

  9. Molecular histology in skin appendage morphogenesis.

    PubMed

    Widelitz, R B; Jiang, T X; Noveen, A; Ting-Berreth, S A; Yin, E; Jung, H S; Chuong, C M

    1997-08-15

    Classical histological studies have demonstrated the cellular organization of skin appendages and helped us appreciate the intricate structures and function of skin appendages. At this juncture, questions can be directed to determine how these cellular organizations are achieved. How do cells rearrange themselves to form the complex cyto-architecture of skin appendages? What are the molecular bases of the morphogenesis and histogenesis of skin appendages? Recently, many new molecules expressed in a spatial and temporal specific manner during the formation of skin appendages were identified by molecular biological approaches. In this review, novel molecular techniques that are useful in skin appendage research are discussed. The distribution of exemplary molecules from different categories including growth factors, intracellular signaling molecules, homeobox genes, adhesion molecules, and extracellular matrix molecules are summarized in a diagram using feather and hair as models. We hope that these results will serve as the ground work for completing the molecular mapping of skin appendages which will refine and re-define our understanding of the developmental process beyond relying on morphological criteria. We also hope that the listed protocols will help those who are interested in this venture. This new molecular histology of skin appendages is the foundation for forming new hypotheses on how molecules are mechanistically involved in skin appendage development and for designing experiments to test them. This may also lead to the modulation of healing and regeneration processes in future treatment modalities. PMID:9297695

  10. Mechanics of Morphogenesis: The Drosophila Eye

    NASA Astrophysics Data System (ADS)

    Hilgenfeldt, Sascha; Gemp, Ian; Carthew, Richard

    2008-11-01

    Epithelial tissues are highly organized layers of individual cells with non-trivial geometry both in equilibrium and during tissue development. In the latter case, individual cell rearrangements and deformations can result in larger-scale, flow-like restructuring. The complex, highly reproducible shapes of epithelial cells in the retina of the Drosophila eye are crucially dependent on the expression of adhesion molecules (cadherins). We show that not only the overall tissue organization, but the shape of each individual cell can be understood through quantitative modeling using minimization of an interfacial energy functional. The model contains only two free parameters, encoding for the adhesion strengths of E- and N-cadherin, and reproduces interfacial angles and lengths to within a few percent accuracy [1]. Characteristic morphological changes in mutant ommatidia can be modeled within this approach, changes that are also present during natural morphogenesis of epithelia. We investigate the role of changing cadherin expression and cytoskeletal tension in these dynamical processes. [1] S. Hilgenfeldt, S. Erisken & R. W. Carthew, Proc. Natl. Acad. Sci. USA 105, 907 (2008)

  11. 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.

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

    PubMed Central

    Frank Eames, B.; 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.

    2010-01-01

    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

  13. A newly established culture method highlights regulatory roles of retinoic acid on morphogenesis and calcification of mammalian limb cartilage.

    PubMed

    Masuda, Eizo; Shirai, Kota; Maekubo, Kenji; Hirai, Yohei

    2015-06-01

    During mammalian embryogenesis, sclerotome-derived chondrocytes in the limb bud are arranged into a complicated bone shape with specific areas undergoing hypertrophy and calcification, creating a region-specific mineralized pattern in the cartilage. To follow chondrogenesis progression in vitro, we isolated limb cartilage from mice on embryonic day 13 (E13) and cultured it at the air-liquid interface after microsurgical removal of the ectoderm/epidermis. Explants underwent proper morphogenesis, giving rise to complete templates for limb bones in vitro. We found that region-specific calcification patterns resembling limbs of prepartum mature embryos could be induced in explants using culture medium containing high concentrations of CaCl2 (Ca), ascorbic acid (AA), and β-glycerophosphoric acid (BGP). In this culture system, excess amounts of all-trans retinoic acid (RA) severely disrupted morphogenesis and calcification patterns in limb cartilage. These effects were more pronounced in forearms than in phalanges. Although dissociated, the nascent chondrocytes in culture did not give rise to cartilage units even though augmented calcification was induced in these cell aggregates in the presence of RA. Taken together, our newly established culture system revealed that RA independently regulates three-dimensional morphogenesis and calcification. PMID:26054768

  14. Computerized tomographic determination of spinal bone mineral content

    NASA Technical Reports Server (NTRS)

    Cann, C. E.; Genant, H. K.

    1980-01-01

    The aims of the study were three-fold: to determine the magnitude of vertebral cancellous mineral loss in normal subjects during bedrest, to compare this loss with calcium balance and mineral loss in peripheral bones, and to use the vertebral measurements as an evaluative criterion for the C12MDP treatment and compare it with other methods. The methods used are described and the results from 14 subjects are presented.

  15. Silicon Nitride: A Synthetic Mineral for Vertebrate Biology.

    PubMed

    Pezzotti, Giuseppe; McEntire, Bryan J; Bock, Ryan; Boffelli, Marco; Zhu, Wenliang; Vitale, Eleonora; Puppulin, Leonardo; Adachi, Tetsuya; Yamamoto, Toshiro; Kanamura, Narisato; Bal, B Sonny

    2016-01-01

    The remarkable stoichiometric flexibility of hydroxyapatite (HAp) enables the formation of a variety of charged structural sites at the material's surface which facilitates bone remodeling due to binding of biomolecule moieties in zwitterionic fashion. In this paper, we report for the first time that an optimized biomedical grade silicon nitride (Si3N4) demonstrated cell adhesion and improved osteoconductivity comparable to highly defective, non-stoichiometric natural hydroxyapatite. Si3N4's zwitterionic-like behavior is a function of the dualism between positive and negative charged off-stoichiometric sites (i.e., N-vacancies versus silanols groups, respectively). Lattice defects at the biomaterial's surface greatly promote interaction with positively- and negatively-charged functional groups in biomolecules, and result in the biologically effective characteristics of silicon nitride. These findings are anticipated to be a starting point for further discoveries of therapeutic bone-graft substitute materials. PMID:27539146

  16. Silicon Nitride: A Synthetic Mineral for Vertebrate Biology

    PubMed Central

    Pezzotti, Giuseppe; McEntire, Bryan J.; Bock, Ryan; Boffelli, Marco; Zhu, Wenliang; Vitale, Eleonora; Puppulin, Leonardo; Adachi, Tetsuya; Yamamoto, Toshiro; Kanamura, Narisato; Bal, B. Sonny

    2016-01-01

    The remarkable stoichiometric flexibility of hydroxyapatite (HAp) enables the formation of a variety of charged structural sites at the material’s surface which facilitates bone remodeling due to binding of biomolecule moieties in zwitterionic fashion. In this paper, we report for the first time that an optimized biomedical grade silicon nitride (Si3N4) demonstrated cell adhesion and improved osteoconductivity comparable to highly defective, non-stoichiometric natural hydroxyapatite. Si3N4’s zwitterionic-like behavior is a function of the dualism between positive and negative charged off-stoichiometric sites (i.e., N-vacancies versus silanols groups, respectively). Lattice defects at the biomaterial’s surface greatly promote interaction with positively- and negatively-charged functional groups in biomolecules, and result in the biologically effective characteristics of silicon nitride. These findings are anticipated to be a starting point for further discoveries of therapeutic bone-graft substitute materials. PMID:27539146

  17. Evolution of vertebrate retinal photoreception

    PubMed Central

    Lamb, Trevor D.

    2009-01-01

    Recent findings shed light on the steps underlying the evolution of vertebrate photoreceptors and retina. Vertebrate ciliary photoreceptors are not as wholly distinct from invertebrate rhabdomeric photoreceptors as is sometimes thought. Recent information on the phylogenies of ciliary and rhabdomeric opsins has helped in constructing the likely routes followed during evolution. Clues to the factors that led the early vertebrate retina to become invaginated can be obtained by combining recent knowledge about the origin of the pathway for dark re-isomerization of retinoids with knowledge of the inability of ciliary opsins to undergo photoreversal, along with consideration of the constraints imposed under the very low light levels in the deep ocean. Investigation of the origin of cell classes in the vertebrate retina provides support for the notion that cones, rods and bipolar cells all originated from a primordial ciliary photoreceptor, whereas ganglion cells, amacrine cells and horizontal cells all originated from rhabdomeric photoreceptors. Knowledge of the molecular differences between cones and rods, together with knowledge of the scotopic signalling pathway, provides an understanding of the evolution of rods and of the rods' retinal circuitry. Accordingly, it has been possible to propose a plausible scenario for the sequence of evolutionary steps that led to the emergence of vertebrate photoreceptors and retina. PMID:19720653

  18. Heterotypic Control of Basement Membrane Dynamics During Branching Morphogenesis

    PubMed Central

    Nelson, Deirdre A.; Larsen, Melinda

    2015-01-01

    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. PMID:25527075

  19. 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.

  20. Prevalent Morphometric Vertebral Fractures in Professional Male Rugby Players

    PubMed Central

    Hind, Karen; Birrell, Fraser; Beck, Belinda

    2014-01-01

    There is an ongoing concern about the risk of injury to the spine in professional rugby players. The objective of this study was to investigate the prevalence of vertebral fracture using vertebral fracture assessment (VFA) dual energy X-ray absorptiometry (DXA) imaging in professional male rugby players. Ninety five professional rugby league (n = 52) and union (n = 43) players (n = 95; age 25.9 (SD 4.3) years; BMI: 29.5 (SD 2.9) kg.m2) participated in the research. Each participant received one VFA, and one total body and lumbar spine DXA scan (GE Lunar iDXA). One hundred and twenty vertebral fractures were identified in over half of the sample by VFA. Seventy four were graded mild (grade 1), 40 moderate (grade 2) and 6 severe (grade 3). Multiple vertebral fractures (≥2) were found in 37 players (39%). There were no differences in prevalence between codes, or between forwards and backs (both 1.2 v 1.4; p>0.05). The most common sites of fracture were T8 (n = 23), T9 (n = 18) and T10 (n = 21). The mean (SD) lumbar spine bone mineral density Z-score was 2.7 (1.3) indicating high player bone mass in comparison with age- and sex-matched norms. We observed a high number of vertebral fractures using DXA VFA in professional rugby players of both codes. The incidence, aetiology and consequences of vertebral fractures in professional rugby players are unclear, and warrant timely, prospective investigation. PMID:24846310

  1. 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

  2. The role of mast cell in tissue morphogenesis. Thymus, duodenum, and mammary gland as examples.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2016-02-01

    Mast cells (MCs) are strategically located at host/environment interfaces like skin, airways, and gastro-intestinal and uro-genital tracts. MCs also populate connective tissues in association with blood and lymphatic vessels and nerves. MCs are absent in avascular tissues, such as mineralized bone, cartilage, and cornea. MCs have various functions and different functional subsets of MCs are encountered in different tissues. However, we do not' know exactly what is the physiological function of MC. Most of these functions are not essential for life, as various MC-deficient strains of mice and rats seems to have normal life spans. In this review article, we have reported and discussed the literature data concerning the role of MCs in tissue morphogenesis, and in particular their role in the development of thymus, duodenum, and mammary gland. PMID:26615957

  3. [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

  4. The Fog signaling pathway: insights into signaling in morphogenesis.

    PubMed

    Manning, Alyssa J; Rogers, Stephen L

    2014-10-01

    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

  5. 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

  6. Directional cell migration, but not proliferation, drives hair placode morphogenesis.

    PubMed

    Ahtiainen, Laura; Lefebvre, Sylvie; Lindfors, Päivi H; Renvoisé, Elodie; Shirokova, Vera; Vartiainen, Maria K; Thesleff, Irma; Mikkola, Marja L

    2014-03-10

    Epithelial reorganization involves coordinated changes in cell shapes and movements. This restructuring occurs during formation of placodes, ectodermal thickenings that initiate the morphogenesis of epithelial organs including hair, mammary gland, and tooth. Signaling pathways in ectodermal placode formation are well known, but the cellular mechanisms have remained ill defined. We established imaging methodology for live visualization of embryonic skin explants during the first wave of hair placode formation. We found that the vast majority of placodal cells were nonproliferative throughout morphogenesis. We show that cell compaction and centripetal migration are the main cellular mechanisms associated with hair placode morphogenesis and that inhibition of actin remodeling suppresses placode formation. Stimulation of both ectodysplasin/NF-κB and Wnt/β-catenin signaling increased cell motility and the number of cells committed to placodal fate. Thus, cell fate choices and morphogenetic events are controlled by the same molecular pathways, providing the framework for coordination of these two processes. PMID:24636260

  7. 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

  8. Built for speed: strain in the cartilaginous vertebral columns of sharks.

    PubMed

    Porter, M E; Diaz, Candido; Sturm, Joshua J; Grotmol, Sindre; Summers, A P; Long, John H

    2014-02-01

    In most bony fishes vertebral column strain during locomotion is almost exclusively in the intervertebral joints, and when these joints move there is the potential to store and release strain energy. Since cartilaginous fishes have poorly mineralized vertebral centra, we tested whether the vertebral bodies undergo substantial strain and thus may be sites of energy storage during locomotion. We measured axial strains of the intervertebral joints and vertebrae in vivo and ex vivo to characterize the dynamic behavior of the vertebral column. We used sonomicrometry to directly measure in vivo and in situ strains of intervertebral joints and vertebrae of Squalus acanthias swimming in a flume. For ex vivo measurements, we used a materials testing system to dynamically bend segments of vertebral column at frequencies ranging from 0.25 to 1.00 Hz and a range of physiologically relevant curvatures, which were determined using a kinematic analysis. The vertebral centra of S. acanthias undergo strain during in vivo volitional movements as well as in situ passive movements. Moreover, when isolated segments of vertebral column were tested during mechanical bending, we measured the same magnitudes of strain. These data support our hypothesis that vertebral column strain in lateral bending is not limited to the intervertebral joints. In histological sections, we found that the vertebral column of S. acanthias has an intracentral canal that is open and covered with a velum layer. An open intracentral canal may indicate that the centra are acting as tunics around some sections of a hydrostat, effectively stiffening the vertebral column. These data suggest that the entire vertebral column of sharks, both joints and centra, is mechanically engaged as a dynamic spring during locomotion. PMID:24388493

  9. 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. PMID:26148971

  10. 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. PMID:21693513

  11. Rapid effects of nitrogen form on leaf morphogenesis in tobacco.

    PubMed

    Walch-Liu, P; Neumann, G; Bangerth, F; Engels, C

    2000-02-01

    Ammonium (NH4+) instead of nitrate (NO3-) as the nitrogen (N) source for tobacco (Nicotiana tabacum L.) cultivated in a pH-buffered nutrient solution resulted in decreased shoot and root biomass. Reduction of shoot fresh weight was mainly related to inhibition of leaf growth, which was already detectable after short-term NH4+ treatments of 24 h, and even at a moderate concentration level of 2 mM. Microscopic analysis of the epidermis of fully expanded leaves revealed a decrease in cell number (50%) and in cell size (30%) indicating that both cell division and cell elongation were affected by NH4+ application. Changes in various physiological parameters known to be associated with NH4(+)-induced growth depression were examined both in long-term and short-term experiments: the concentrations of total N, soluble sugars and starch as well as the osmotic potential, the apparent hydraulic conductivity and the rate of water uptake were not reduced by NH4+ treatments (duration 1-12 d), suggesting that leaf growth was neither limited by the availability of N and carbohydrates, nor by a lack of osmotica or water supply. Although the concentration of K+ in leaf press sap declined in expanding leaves by approximately 15% in response to NH4+ nutrition, limitation of mineral nutrients seems to be unlikely in view of the fast response of leaf growth at 24 h after the start of the NH4+ treatment. No inhibitory effects were observed when NH4+ and NO3- were applied simultaneously (each 1 mM) resulting in a NO3-/NH4+ net uptake ratio of 6:4. These findings suggest that the rapid inhibition of leaf growth was not primarily related to NH4+ toxicity, but to the lack of NO3(-)-supply. Growth inhibition of plants fed solely with NH4+ was associated with a 60% reduction of the zeatine + zeatine riboside (Z + ZR) cytokinin fraction in the xylem sap after 24 h. Furthermore Z + ZR levels declined to almost zero within the next 4 d after start of the NH4+ treatment. In contrast, the

  12. [Joint morphogenesis and development of permanent articular cartilage].

    PubMed

    Ohta, Yoichi; Iwamoto, Masahiro

    2011-06-01

    During limb skeletogenesis progenitor mesenchymal cells aggregate at specific times and sites to form continuous precartilaginous condensations. With time the condensations undergo chondrogenesis and give rise to cartilaginous anlagen that exhibit incipient synovial joints at each end. A multitude of factors regulates subdivision into discrete skeletal elements and the formation, organization, morphogenesis and structure of the joints. This review summarizes recent advance of joint morphogenesis and actions of key players of joint and articular cartilage formation. In addition, we would like to discuss possible direction to translate basic research findings towards treatment of joint diseases. PMID:21628794

  13. 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

  14. Collective Epithelial Migration and Cell Rearrangements Drive Mammary Branching Morphogenesis

    PubMed Central

    Ewald, Andrew J.; Brenot, Audrey; Duong, Myhanh; Chan, Bianca S.; Werb, Zena

    2009-01-01

    Summary Epithelial organs are built through the movement of groups of interconnected cells. We observed cells in elongating mammary ducts reorganize into a multilayered epithelium, migrate collectively, and rearrange dynamically, all without forming leading cellular extensions. Duct initiation required proliferation, Rac, and myosin light-chain kinase, whereas repolarization to a bilayer depended on Rho kinase. We observed that branching morphogenesis results from the active motility of both luminal and myoepithelial cells. Luminal epithelial cells advanced collectively, whereas myoepithelial cells appeared to restrain elongating ducts. Significantly, we observed that normal epithelium and neoplastic hyperplasias are organized similarly during morphogenesis, suggesting common mechanisms of epithelial growth. PMID:18410732

  15. Modeling mammary gland morphogenesis as a reaction-diffusion process.

    PubMed

    Grant, Mark R; Hunt, C Anthony; Xia, Lan; Fata, Jimmie E; Bissell, Mina J

    2004-01-01

    Mammary ducts are formed through a process of branching morphogenesis. We present results of experiments using a simulation model of this process, and discuss their implications for understanding mammary duct extension and bifurcation. The model is a cellular automaton approximation of a reaction-diffusion process in which matrix metalloproteinases represent the activator, inhibitors of matrix metalloproteinases represent the inhibitor, and growth factors serve as a substrate. We compare results from the simulation model with those from in-vivo experiments as part of an assessment of whether duct extension and bifurcation during morphogenesis may be a consequence of a reaction-diffusion mechanism mediated by MMPs and TIMPs. PMID:17271768

  16. 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…

  17. Kinesin-related proteins in the mammalian testes: candidate motors for meiosis and morphogenesis.

    PubMed Central

    Sperry, A O; Zhao, L P

    1996-01-01

    The kinesin superfamily of molecular motors comprises proteins that participate in a wide variety of motile events within the cell. Members of this family share a highly homologous head domain responsible for force generation attached to a divergent tail domain thought to couple the motor domain to its target cargo. Many kinesin-related proteins (KRPs) participate in spindle morphogenesis and chromosome movement in cell division. Genetic analysis of mitotic KRPs in yeast and Drosophila, as well as biochemical experiments in other species, have suggested models for the function of KRPs in cell division, including both mitosis and meiosis. Although many mitotic KRPs have been identified, the relationship between mitotic motors and meiotic function is not clearly understood. We have used sequence similarity between mitotic KRPs to identify candidates for meiotic and/or mitotic motors in a vertebrate. We have identified a group of kinesin-related proteins from rat testes (termed here testes KRP1 through KRP6) that includes new members of the bimC and KIF2 subfamilies as well as proteins that may define new kinesin subfamilies. Five of the six testes KRPs identified are expressed primarily in testes. Three of these are expressed in a region of the seminiferous epithelia (SE) rich in meiotically active cells. Further characterization of one of these KRPs, KRP2, showed it to be a promising candidate for a motor in meiosis: it is localized to a meiotically active region of the SE and is homologous to motor proteins associated with the mitotic apparatus. Testes-specific genes provide the necessary probes to investigate whether the motor proteins that function in mammalian meiosis overlap with those of mitosis and whether motor proteins exist with functions unique to meiosis. Our search for meiotic motors in a vertebrate testes has successfully identified proteins with properties consistent with those of meiotic motors in addition to uncovering proteins that may function in

  18. Vertebral Augmentation for Osteoporotic Compression Fractures.

    PubMed

    Richmond, Bradford J

    2016-01-01

    Vertebral augmentation procedures such as vertebroplasty and kyphoplasty were developed to reduce pain and improve quality of life for patients with osteoporotic vertebral compression fractures. However, the use of vertebral augmentation has been debated and questioned since its inception. This article addresses some of these issues. PMID:26490134

  19. 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. PMID:25662266

  20. 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

  1. 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.

  2. 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

  3. Mineral Chart

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Mineral Chart KidsHealth > For Teens > Mineral Chart Print A A A Text Size en ... sources of calcium. You'll also find this mineral in broccoli and dark green, leafy vegetables. Soy ...

  4. Mineral oils

    NASA Technical Reports Server (NTRS)

    Furby, N. W.

    1973-01-01

    The characteristics of lubricants made from mineral oils are discussed. Types and compositions of base stocks are reviewed and the product demands and compositions of typical products are outlined. Processes for commercial production of mineral oils are examined. Tables of data are included to show examples of product types and requirements. A chemical analysis of three types of mineral oils is reported.

  5. Eavesdropping on the cytoskeleton: progress and controversy in the yeast morphogenesis checkpoint.

    PubMed

    Keaton, Mignon A; Lew, Daniel J

    2006-12-01

    The morphogenesis checkpoint provides a link between bud formation and mitosis in yeast. In this pathway, insults affecting the actin or septin cytoskeleton trigger a cell cycle arrest, mediated by the Wee1 homolog Swe1p, which catalyzes the inhibitory phosphorylation of the mitosis-promoting cyclin-dependent kinase (CDK) on a conserved tyrosine residue. Analyses of Swe1p phosphorylation have mapped 61 sites targeted by CDKs and Polo-related kinases, which control both Swe1p activity and Swe1p degradation. Although the sites themselves are not evolutionarily conserved, the control of Swe1p degradation exhibits many conserved features, and is linked to DNA-responsive checkpoints in vertebrate cells. At the 'sensing' end of the checkpoint, recent work has begun to shed light on how septins are organized and how they impact Swe1p regulators. However, the means by which Swe1p responds to actin perturbations once a bud has formed remains controversial. PMID:17055334

  6. Matrix--mineral relationships in enamel tissues.

    PubMed

    Fearnhead, R W

    1979-03-01

    A personal view of vertebrate enamels and their matrix-mineral relationships is given by first considering enamel types and speculating on the nature, distribution, formation and role of enamel protein. Not all the work consulted is mentioned in the text. The additional works are, however, included in the list of references. PMID:283133

  7. The temporal dynamics of vertebrate limb development, teratogenesis and evolution.

    PubMed

    Zeller, Rolf

    2010-08-01

    Recent genetic and functional analysis of vertebrate limb development begins to reveal how the functions of particular genes and regulatory hierarchies can drastically change over time. The temporal and spatial interplay of the two instructive signalling centres are part of a larger signalling system that orchestrates limb bud morphogenesis in a rather self-regulatory manner. It appears that mesenchymal cells are specified early and subsequently, the progenitors for the different skeletal elements are expanded and determined progressively during outgrowth. Mutations and teratogens that disrupt distal progression of limb development most often cause death of the early-specified progenitors rather than altering their fates. The proliferative expansion and distal progression of paired appendage development was one of the main driving forces behind the transition from fin to limb buds during paired appendage evolution. Finally, the adaptive diversification or loss of modern tetrapod limbs in particular phyla or species appear to be a consequence of evolutionary tampering with the regulatory systems that control distal progression of limb development. PMID:20537528

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Vertebral Fractures: Clinical Importance and Management.

    PubMed

    Kendler, D L; Bauer, D C; Davison, K S; Dian, L; Hanley, D A; Harris, S T; McClung, M R; Miller, P D; Schousboe, J T; Yuen, C K; Lewiecki, E M

    2016-02-01

    Vertebral fractures are common and can result in acute and chronic pain, decreases in quality of life, and diminished lifespan. The identification of vertebral fractures is important because they are robust predictors of future fractures. The majority of vertebral fractures do not come to clinical attention. Numerous modalities exist for visualizing suspected vertebral fracture. Although differing definitions of vertebral fracture may present challenges in comparing data between different investigations, at least 1 in 5 men and women aged >50 years have one or more vertebral fractures. There is clinical guidance to target spine imaging to individuals with a high probability of vertebral fracture. Radiology reports of vertebral fracture need to clearly state that the patient has a "fracture," with further pertinent details such as the number, recency, and severity of vertebral fracture, each of which is associated with risk of future fractures. Patients with vertebral fracture should be considered for antifracture therapy. Physical and pharmacologic modalities of pain control and exercises or physiotherapy to maintain spinal movement and strength are important components in the care of vertebral fracture patients. PMID:26524708

  14. 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

  15. Roles of Bmp4 during tooth morphogenesis and sequential tooth formation

    PubMed Central

    Jia, Shihai; Zhou, Jing; Gao, Yang; Baek, Jin-A; Martin, James F.; Lan, Yu; Jiang, Rulang

    2013-01-01

    Previous studies have suggested that Bmp4 is a key Msx1-dependent mesenchymal odontogenic signal for driving tooth morphogenesis through the bud-to-cap transition. Whereas all tooth germs were arrested at the bud stage in Msx1–/– mice, we show that depleting functional Bmp4 mRNAs in the tooth mesenchyme, through neural crest-specific gene inactivation in Bmp4f/f;Wnt1Cre mice, caused mandibular molar developmental arrest at the bud stage but allowed maxillary molars and incisors to develop to mineralized teeth. We found that expression of Osr2, which encodes a zinc finger protein that antagonizes Msx1-mediated activation of odontogenic mesenchyme, was significantly upregulated in the molar tooth mesenchyme in Bmp4f/f;Wnt1Cre embryos. Msx1 heterozygosity enhanced maxillary molar developmental defects whereas Osr2 heterozygosity partially rescued mandibular first molar morphogenesis in Bmp4f/f;Wnt1Cre mice. Moreover, in contrast to complete lack of supernumerary tooth initiation in Msx1–/–Osr2–/– mice, Osr2–/–Bmp4f/f;Wnt1Cre compound mutant mice exhibited formation and subsequent arrest of supernumerary tooth germs that correlated with downregulation of Msx1 expression in the tooth mesenchyme. In addition, we found that the Wnt inhibitors Dkk2 and Wif1 were much more abundantly expressed in the mandibular than maxillary molar mesenchyme in wild-type embryos and that Dkk2 expression was significantly upregulated in the molar mesenchyme in Bmp4f/f;Wnt1Cre embryos, which correlated with the dramatic differences in maxillary and mandibular molar phenotypes in Bmp4f/f;Wnt1Cre mice. Together, these data indicate that Bmp4 signaling suppresses tooth developmental inhibitors in the tooth mesenchyme, including Dkk2 and Osr2, and synergizes with Msx1 to activate mesenchymal odontogenic potential for tooth morphogenesis and sequential tooth formation. PMID:23250216

  16. p120-catenin-dependent junctional recruitment of Shroom3 is required for apical constriction during lens pit morphogenesis

    PubMed Central

    Lang, Richard A.; Herman, Ken; Reynolds, Albert B.; Hildebrand, Jeffrey D.; Plageman, Timothy F.

    2014-01-01

    Apical constriction (AC) is a widely utilized mechanism of cell shape change whereby epithelial cells transform from a cylindrical to conical shape, which can facilitate morphogenetic movements during embryonic development. Invertebrate epithelial cells undergoing AC depend on the contraction of apical cortex-spanning actomyosin filaments that generate force on the apical junctions and pull them toward the middle of the cell, effectively reducing the apical circumference. A current challenge is to determine whether these mechanisms are conserved in vertebrates and to identify the molecules responsible for linking apical junctions with the AC machinery. Utilizing the developing mouse eye as a model, we have uncovered evidence that lens placode AC may be partially dependent on apically positioned myosin-containing filaments associated with the zonula adherens. In addition we found that, among several junctional components, p120-catenin genetically interacts with Shroom3, a protein required for AC during embryonic morphogenesis. Further analysis revealed that, similar to Shroom3, p120-catenin is required for AC of lens cells. Finally, we determined that p120-catenin functions by recruiting Shroom3 to adherens junctions. Together, these data identify a novel role for p120-catenin during AC and further define the mechanisms required for vertebrate AC. PMID:25038041

  17. 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

  18. biniou (FoxF), a central component in a regulatory network controlling visceral mesoderm development and midgut morphogenesis in Drosophila

    PubMed Central

    Zaffran, Stephane; Küchler, Axel; Lee, Hsiu-Hsiang; Frasch, Manfred

    2001-01-01

    The subdivision of the lateral mesoderm into a visceral (splanchnic) and a somatic layer is a crucial event during early mesoderm development in both arthropod and vertebrate embryos. In Drosophila, this subdivision leads to the differential development of gut musculature versus body wall musculature. Here we report that biniou, the sole Drosophila representative of the FoxF subfamily of forkhead domain genes, has a key role in the development of the visceral mesoderm and the derived gut musculature. biniou expression is activated in the trunk visceral mesoderm primordia downstream of dpp, tinman, and bagpipe and is maintained in all types of developing gut muscles. We show that biniou activity is essential for maintaining the distinction between splanchnic and somatic mesoderm and for differentiation of the splanchnic mesoderm into midgut musculature. biniou is required not only for the activation of differentiation genes that are expressed ubiquitously in the trunk visceral mesoderm but also for the expression of dpp in parasegment 7, which governs proper midgut morphogenesis. Activation of dpp is mediated by specific Biniou binding sites in a dpp enhancer element, which suggests that Biniou serves as a tissue-specific cofactor of homeotic gene products in visceral mesoderm patterning. Based upon these and other data, we propose that the splanchnic mesoderm layers in Drosophila and vertebrate embryos are homologous structures whose development into gut musculature and other visceral organs is critically dependent on FoxF genes. PMID:11691840

  19. High Incidence of Vertebral Fractures in Children with Acute Lymphoblastic Leukemia 12 Months After the Initiation of Therapy

    PubMed Central

    Alos, Nathalie; Grant, Ronald; Ramsay, Timothy; Halton, Jacqueline; Cummings, Elizabeth A.; Miettunen, Paivi M.; Abish, Sharon; Atkinson, Stephanie; Barr, Ronald; Cabral, David A.; Cairney, Elizabeth; Couch, Robert; Dix, David B.; Fernandez, Conrad V.; Hay, John; Israels, Sara; Laverdière, Caroline; Lentle, Brian; Lewis, Victor; Matzinger, MaryAnn; Rodd, Celia; Shenouda, Nazih; Stein, Robert; Stephure, David; Taback, Shayne; Wilson, Beverly; Williams, Kathryn; Rauch, Frank; Siminoski, Kerry; Ward, Leanne M.

    2014-01-01

    Purpose Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been reported. Patient and Methods We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semi-quantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral fractures. Results Of the 155 children, 25 (16%, 95% Confidence Interval (CI) 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen of the 25 children with incident vertebral fractures (52%) also had fractures at baseline. Vertebral fractures at baseline increased the odds of an incident fracture at 12 months by an odds ratio of 7.3 (95% CI 2.3 to 23.1, p = 0.001). In addition, for every one standard deviation reduction in spine BMD Z-score at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI 1.2 to 2.7, p = 0.006). Conclusion Children with ALL have a high incidence of vertebral fractures after 12 months of chemotherapy, and the presence of vertebral fractures and reductions in spine BMD Z-scores at baseline are highly associated clinical features. PMID:22734031

  20. Pharyngeal morphogenesis requires fras1-itga8-dependent epithelial-mesenchymal interaction.

    PubMed

    Talbot, Jared Coffin; Nichols, James T; Yan, Yi-Lin; Leonard, Isaac F; BreMiller, Ruth A; Amacher, Sharon L; Postlethwait, John H; Kimmel, Charles B

    2016-08-01

    Both Fras1 and Itga8 connect mesenchymal cells to epithelia by way of an extracellular 'Fraser protein complex' that functions in signaling and adhesion; these proteins are vital to the development of several vertebrate organs. We previously found that zebrafish fras1 mutants have craniofacial defects, specifically, shortened symplectic cartilages and cartilage fusions that spare joint elements. During a forward mutagenesis screen, we identified a new zebrafish mutation, b1161, that we show here disrupts itga8, as confirmed using CRISPR-generated itga8 alleles. fras1 and itga8 single mutants and double mutants have similar craniofacial phenotypes, a result expected if loss of either gene disrupts function of the Fraser protein complex. Unlike fras1 mutants or other Fraser-related mutants, itga8 mutants do not show blistered tail fins. Thus, the function of the Fraser complex differs in the craniofacial skeleton and the tail fin. Focusing on the face, we find that itga8 mutants consistently show defective outpocketing of a late-forming portion of the first pharyngeal pouch, and variably express skeletal defects, matching previously characterized fras1 mutant phenotypes. In itga8 and fras1 mutants, skeletal severity varies markedly between sides, indicating that both mutants have increased developmental instability. Whereas fras1 is expressed in epithelia, we show that itga8 is expressed complementarily in facial mesenchyme. Paired with the observed phenotypic similarity, this expression indicates that the genes function in epithelial-mesenchymal interactions. Similar interactions between Fras1 and Itga8 have previously been found in mouse kidney, where these genes both regulate Nephronectin (Npnt) protein abundance. We find that zebrafish facial tissues express both npnt and the Fraser gene fibrillin2b (fbn2b), but their transcript levels do not depend on fras1 or itga8 function. Using a revertible fras1 allele, we find that the critical window for fras1 function in

  1. 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

  2. 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

  3. SOX17 links gut endoderm morphogenesis and germ layer segregation.

    PubMed

    Viotti, Manuel; Nowotschin, Sonja; Hadjantonakis, Anna-Katerina

    2014-12-01

    Gastrulation leads to three germ layers--ectoderm, mesoderm and endoderm--that are separated by two basement membranes. In the mouse embryo, the emergent gut endoderm results from the widespread intercalation of cells of two distinct origins: pluripotent epiblast-derived definitive endoderm (DE) and extra-embryonic visceral endoderm (VE). Here we image the trajectory of prospective DE cells before intercalating into the VE epithelium. We show that the transcription factor SOX17, which is activated in prospective DE cells before intercalation, is necessary for gut endoderm morphogenesis and the assembly of the basement membrane that separates gut endoderm from mesoderm. Our results mechanistically link gut endoderm morphogenesis and germ layer segregation, two central and conserved features of gastrulation. PMID:25419850

  4. The evolution of fungal morphogenesis, a personal account.

    PubMed

    Bartnicki-Garcia, Salomon

    2016-01-01

    This article describes the evolution of the field of fungal morphogenesis, its beginning at the end of the 19th century and its exponential growth during the second half of the 20th century, continuing until the present day. The main theme correlates biological progress with the advent of new technologies. Accordingly the article describes the discovery of apical growth, the fibrillar nature of the fungal wall, the chemistry of the cell wall, the search for biochemical pathways in morphogenesis, the discovery of the Spitzenkörper, the apical gradient of wall synthesis, key highlights in ultrastructural research, the development of mathematical models particularly the vesicle supply center (VSC) model, the revolution brought about by molecular biology and unique discoveries such as the hydrophobins and γ-tubulin and some the latest triumphs of the marriage between molecular genetics and confocal microscopy. Credit is given to the investigators responsible for all the advances. PMID:26951367

  5. Yeast and Fungal Morphogenesis: Evolution of Morphologic Diversity

    PubMed Central

    Wedlich-Soldner, Roland; Li, Rong

    2008-01-01

    Cellular morphogenesis is a complex process and molecular studies in the last few decades have amassed a large amount of information that is difficult to grasp in any completeness. Fungal systems, in particular the budding and fission yeasts, have been important players in unravelling the basic structural and regulatory elements involved in a wide array of cellular processes. In this article, we address the design principles underlying the various processes of yeast and fungal morphogenesis. We attempt to explain the apparent molecular complexity from the perspective of the evolutionary theory of “facilitated variation”. Following a summary of some of the most studied morphogenetic phenomena, we discuss, using recent examples, the underlying core processes and their associated “weak” regulatory linkages that bring about variation in morphogenetic phenotypes. PMID:18299240

  6. Polarized Protein Transport and Lumen Formation During Epithelial Tissue Morphogenesis

    PubMed Central

    Blasky, Alex J.; Mangan, Anthony; Prekeris, Rytis

    2015-01-01

    One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best-studied model of this process is the cross talk between individual epithelial cells during their polarization to form the multicellular epithelial lumen during tissue morphogenesis. Multiple mechanisms of apical lumen formation have been proposed. Some epithelial lumens form from preexisting polarized epithelial structures. However, de novo lumen formation from nonpolarized cells has recently emerged as an important driver of epithelial tissue morphogenesis, especially during the formation of small epithelial tubule networks. In this review, we discuss the latest findings regarding the mechanisms and regulation of de novo lumen formation in vitro and in vivo. PMID:26359775

  7. Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis.

    PubMed

    Swinehart, Ilea T; Badylak, Stephen F

    2016-03-01

    During normal morphogenesis the extracellular matrix (ECM) influences cell motility, proliferation, apoptosis, and differentiation. Tissue engineers have attempted to harness the cell signaling potential of ECM to promote the functional reconstruction, if not regeneration, of injured or missing adult tissues that otherwise heal by the formation of scar tissue. ECM bioscaffolds, derived from decellularized tissues, have been used to promote the formation of site appropriate, functional tissues in many clinical applications including skeletal muscle, fibrocartilage, lower urinary tract, and esophageal reconstruction, among others. These scaffolds function by the release or exposure of growth factors and cryptic peptides, modulation of the immune response, and recruitment of progenitor cells. Herein, we describe this process of ECM induced constructive remodeling and examine similarities to normal tissue morphogenesis. PMID:26699796

  8. 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

  9. 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

  10. 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

  11. The microenvironmental determinants for kidney epithelial cyst morphogenesis

    PubMed Central

    Guo, Qiusha; Xia, Bing; Moshiach, Simon; Xu, Congfeng; Jiang, Yongde; Chen, Yuanjian; Sun, Yao; Lahti, Jill M.; Zhang, Xin A.

    2011-01-01

    Although epithelial morphogenesis is tightly controlled by intrinsic genetic programs, the microenvironment in which epithelial cells proliferate and differentiate also contributes to the morphogenetic process. The roles of the physical microenvironment in epithelial morphogenesis, however, have not been well dissected. In this study, we assessed the impact of the microenvironment on epithelial cyst formation, which often marks the beginning or end step of morphogenesis of epithelial tissues and the pathological characteristic of some diseases. Previous studies have demonstrated that Madin-Darby canine kidney (MDCK) epithelial cells form cysts when grown in a three-dimensional (3D) extracellullar matrix (ECM) environment. We have now further demonstrated that the presence of ECM in the 3D scaffold is required for the formation of properly polarized cysts. Also, we have found that the full interface of epithelial cells with the ECM environment (in-3D) is not essential for cyst formation, since partial contact (on-3D) is sufficient to induce cystogenesis. In addition, we have defined the minimal ECM environment or the physical threshold for cystogenesis under the on-3D condition. Only above the threshold can the morphological cues from the ECM environment induce cyst formation. Moreover, cyst formation under the on-3D condition described in this study actually defines a novel and more feasible model to analyze in vitro morphogenesis. Finally, we have found that, during cystogenesis, MDCK cells generate basal microprotrusions and produce vesicle-like structures to the basal extracellular space, which are specific to and correlated with cyst formation. For the first time, we have systematically elucidated the microenvironmental determinants for epithelial cystogenesis. PMID:18191498

  12. 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.

  13. 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.

  14. Heparan sulfate in lung morphogenesis: The elephant in the room.

    PubMed

    Thompson, Sophie M; Jesudason, Edwin C; Turnbull, Jeremy E; Fernig, David G

    2010-03-01

    Heparan sulfate (HS) is a structurally complex polysaccharide located on the cell surface and in the extracellular matrix, where it participates in numerous biological processes through interactions with a vast number of regulatory proteins such as growth factors and morphogens. HS is crucial for lung development; disruption of HS synthesis in flies and mice results in a major aberration of airway branching, and in mice, it results in neonatal death as a consequence of malformed lungs and respiratory distress. Epithelial-mesenchymal interactions governing lung morphogenesis are directed by various diffusible proteins, many of which bind to, and are regulated by HS, including fibroblast growth factors, sonic hedgehog, and bone morphogenetic proteins. The majority of research into the molecular mechanisms underlying defective lung morphogenesis and pulmonary pathologies, such as bronchopulmonary dysplasia and pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH), has focused on abnormal protein expression. The potential contribution of HS to abnormalities of lung development has yet to be explored to any significant extent, which is somewhat surprising given the abnormal lung phenotype exhibited by mutant mice synthesizing abnormal HS. This review summarizes our current understanding of the role of HS and HS-binding proteins in lung morphogenesis and will present in vitro and in vivo evidence for the fundamental importance of HS in airway development. Finally, we will discuss the future possibility of HS-based therapeutics for ameliorating insufficient lung growth associated with lung diseases such as CDH. PMID:20301217

  15. 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

  16. 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

  17. 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

  18. Industrial Minerals.

    ERIC Educational Resources Information Center

    Brady, Lawrence L.

    1983-01-01

    Discusses trends in and factors related to the production of industrial minerals during 1982, indicating that, as 1981 marked a downturn in production of industrial minerals, 1982 continued the trend with temporary and permanent cutbacks in mine and plant production. Includes highlights of several conferences/conference papers in this field.…

  19. The expression patterns of heat shock genes and proteins and their role during vertebrate's development.

    PubMed

    Rupik, Weronika; Jasik, Krzysztof; Bembenek, Jadwiga; Widłak, Wiesława

    2011-08-01

    Highly evolutionary conserved heat shock proteins (HSPs) act as molecular chaperones in regulation of cellular homeostasis and promoting survival. Generally they are induced by a variety of stressors whose effect could be disastrous on the organism, but they are also widely constitutively expressed in the absence of stress. Varied HSP expressions seem to be very essential in the critical steps of embryonic and extra-embryonic structures formation and may correspond to cell movements, proliferation, morphogenesis and apoptosis, which occur during embryonic development. While our knowledge of detailed HSP expression patterns is in constant progress, their functions during embryonic development are not yet fully understood. In the paper, we review available data on HSP expression and discuss their role during vertebrate development. PMID:21527352

  20. Variance in the treatment of vertebral haemangiomas.

    PubMed

    Rawat, Sheh; Nangia, S; Ezhilalan, R B; Bansal, A K; Ghosh, D

    2007-01-01

    Vertebral haemangiomas constitute an infrequently encounterd entity in clinical practice. Although x-ray, computerised tomography scan and magnetic resonance Imaging scan provide a pathognomic picture confirming the diagnosis of vertebral haemangiomas, angiography constitutes an important tool for diagnosis and helps in deciding and execution of treatment. Various treatment modalities like surgery, radiotherapy, pre-operative embolisation, percutaneous vertebroplasty and intralesional ethanol have been discussed in the setting of asymptomatic vertebral haemangiomas to those presenting with features of cord compression. PMID:17802977

  1. Evolutionary Specialization of Tactile Perception in Vertebrates.

    PubMed

    Schneider, Eve R; Gracheva, Elena O; Bagriantsev, Slav N

    2016-05-01

    Evolution has endowed vertebrates with the remarkable tactile ability to explore the world through the perception of physical force. Yet the sense of touch remains one of the least well understood senses at the cellular and molecular level. Vertebrates specializing in tactile perception can highlight general principles of mechanotransduction. Here, we review cellular and molecular adaptations that underlie the sense of touch in typical and acutely mechanosensitive vertebrates. PMID:27053733

  2. CT-derived finite element models to determine vertebral cortex strength

    NASA Astrophysics Data System (ADS)

    Faulkner, Ken G.; Cann, Christopher E.; Hasegawa, Bruce H.

    1990-07-01

    The contribution of the vertebral cortex to the strength of the vertebrae is unknown. Several researchers have attempted to estimate this contribution by mechanically testing excised vertebral specimens. We have addressed the problem by creating finite element models (FEM) of the lumbar spine from contiguous scan CT studies. Seventeen women with no evidence of spinal fracture were scanned on a commercial CT scanner along with a calibration phantom to allow accurate determination of spinal bone mineral density. Using interactive software techniques two vertebral FEM are created from each scan set one with the cortex intact and the second with the cortical shell removed. Each model was analyzed under compression using finite element software and the results were compared for the intact and no cortex cases. Removal of the cortical shell was found to significantly decrease vertebral strength an average of 15. 6 3. 0 (mean standard error of the mean) in our study (p 0. 001). The decrease was variable between patients and did not appear related to trabecular mineral density. In osteoporotic patients the cortical contribution to vertebral strength may be much greater than that reported for the normal women due to the accelerated loss of trabecular bone. 1.

  3. General management of vertebral fractures.

    PubMed

    Rapado, A

    1996-03-01

    Vertebral fractures cause pain and disability. Four concepts should guide their comprehensive management: treat the patient, not the skeleton; use a multidisciplinary approach; engage the patient and his or her family in the treatment; and provide appropriate goals, education, encouragement, and support. The goals include procuring bone mass and preventing injury: back support, physical therapy, occupational therapy, psychosocial support, and prevention of falls. Initial treatment includes bed rest, pain management with local and systemic analgesia, bracing to improve comfort, and patient reassurance. Long-term management includes spinal stretching exercises and continuing ordinary activities within limits permitted by pain. A back school program is an effective addition to conventional concepts using physiotherapy exclusively. In certain selected patients, the indication for operative treatment of vertebral fracture depends on the additional injury, and extent and characteristics of cord compression; stability of the fracture; and the amount of deformity. Vertebroplasty can be effective in the control of pain and in obtaining stability of the spine. PMID:8777087

  4. 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

  5. Height Restoration after Balloon Kyphoplasty in Rheumatoid Patients with Osteoporotic Vertebral Compression Fracture

    PubMed Central

    Suh, Seung-Pyo; Kim, Chul-Woong; Jo, Young-Hoon

    2015-01-01

    Study Design Retrospective study. Purpose This study was conducted to compare vertebral body height restoration rate in rheumatoid arthritis (RA) patients who had undergone percutaneous balloon kyphoplasty (KP) with that of control group who had matched age, sex, body mass index, and bone mineral density. Overview of Literature There is no report on result of KP in RA patients. Methods Postoperative height restoration rate of RA group consisting of 15 patients (18 vertebral bodies) who had undergone KP due to osteoporotic vertebral compression fracture with a 30% or higher vertebral compression rate between May 2005 and January 2013 were compared to control group consisting of 38 patients (39 vertebral bodies) who had matched age, sex, body mass index, and bone mineral density. Results No statically significant difference in age (p=0.846), sex (p=0.366), body mass index (p=0.826), bone mineral density (p=0.349), time to surgery (p=0.528), polymethylmethacrylate injection time (p=0.298), or amount (p=0.830) was found between the RA group and the control group. However, preoperative compression rate in the RA group was significantly (p=0.025) higher compared to that in the control group. In addition, postoperative height restoration rate showed significant correlation with the RA group (p=0.008). Although higher incidence of recollapse occurred in the RA group compared to that in the control group, the difference was not statistically significant (p=0.305). Conclusions Compared to the control group, RA patients showed higher compression rate and higher vertebral restoration rate after KP, indirectly indicating weaker bone quality in patients with RA. Higher incidence of recollapse occurred in the RA group compared to that in the control group, although it was not statistically significant. PMID:26240718

  6. Relationship Between BMD and Prevalent Vertebral Fractures in Indian Women Older Than 50 Yr.

    PubMed

    Gupta, Yashdeep; Marwaha, Raman K; Kukreja, Subhash; Bhadra, Kuntal; Narang, Archana; Mani, Kalaivani; Mithal, Ambrish; Tandon, Nikhil

    2016-01-01

    The purpose of the study was to study the relationship of morphometric vertebral fractures with bone mineral density (BMD) in Indian women older than 50 yr. Four hundred fifteen healthy Indian women older than 50 yr (mean age: 62.8 yr) underwent lateral X-rays of the lumbar and thoracic spine. Genant's semiquantitative method was used to diagnose and classify morphometric vertebral fractures. BMD was measured by DXA at lumbar spine and total hip. Recruited subjects underwent anthropometric, biochemical, and hormonal evaluation. Vertebral fractures were present in 17.1% (95% confidence interval: 13.5, 20.8) subjects. Prevalence of osteoporosis based on BMD was 35.7%. By adding those with prevalent fractures, the number of women requiring therapy for osteoporosis would increase to 46.5%. The BMD measured at femur neck, total hip, and lumbar spine (L1eL4) was not found to be lower in women with vertebral fractures as compared with those without fractures. BMD was not found to be lower in women with vertebral fractures as compared with those without fractures. Significant number of additional subjects with BMD in the normal or osteopenic range become eligible for osteoporosis treatment when presence of vertebral fracture is used as an independent indication for such treatment. PMID:26050877

  7. Thoracic kyphosis and rate of incident vertebral fractures: the Fracture Intervention Trial

    PubMed Central

    Vittinghoff, E.; Kado, D. M.; Lane, N. E.; Ensrud, K. E.; Shipp, K.

    2016-01-01

    Summary Biomechanical analyses support the theory that thoracic spine hyperkyphosis may increase risk of new vertebral fractures. While greater kyphosis was associated with an increased rate of incident vertebral fractures, our analysis does not show an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture. Introduction Biomechanical analyses suggest hyperkyphosis may increase risk of incident vertebral fracture by increasing the load on vertebral bodies during daily activities. We propose to assess the association of kyphosis with incident radiographic vertebral fracture. Methods We used data from the Fracture Intervention Trial among 3038 women 55–81 years of age with low bone mineral density (BMD). Baseline kyphosis angle was measured using a Debrunner kyphometer. Vertebral fractures were assessed at baseline and follow-up from lateral radiographs of the thoracic and lumbar spine. We used Poisson models to estimate the independent association of kyphosis with incident fracture, controlling for age and femoral neck BMD. Results Mean baseline kyphosis was 48° (SD = 12) (range 7–83). At baseline, 962 (32 %) participants had a prevalent fracture. There were 221 incident fractures over a median of 4 years. At baseline, prevalent fracture was associated with 3.7° greater average kyphosis (95 % CI 2.8–4.6, p < 0.0005), adjusting for age and femoral neck BMD. Before adjusting for prevalent fracture, each 10° greater kyphosis was associated with 22 % increase (95 % CI 8–38 %, p = 0.001) in annualized rate of new radiographic vertebral fracture, adjusting for age and femoral neck BMD. After additional adjustment for prevalent fracture, estimated increased annualized rate was attenuated and no longer significant, 8 % per 10° kyphosis (95 % CI −4 to 22 %, p = 0.18). Conclusions While greater kyphosis increased the rate of

  8. 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'.

  9. 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

  10. Mineral Quantification.

    PubMed

    2016-01-01

    Optimal intakes of elements, such as sodium, potassium, magnesium, calcium, manganese, copper, zinc and iodine, can reduce individual risk factors including those related to cardiovascular diseases among humans and animals. In order to meet the need for vitamins, major minerals, trace minerals, fatty acids and amino acids, it is necessary to include a full spectrum programme that can deliver all of the nutrients in the right ratio. Minerals are required for normal growth, activities of muscles, skeletal development (such as calcium), cellular activity, oxygen transport (copper and iron), chemical reactions in the body, intestinal absorption (magnesium), fluid balance and nerve transmission (sodium and potassium), as well as the regulation of the acid base balance (phosphorus). The chapter discusses the chemical and instrumentation techniques used for estimation of minerals such as N, P, Ca, Mg, K, Na, Fe, Cu, Zn, B and Mb. PMID:26939263

  11. Sex hormones, sex hormone binding globulin, and vertebral fractures in older men.

    PubMed

    Cawthon, Peggy M; Schousboe, John T; Harrison, Stephanie L; Ensrud, Kristine E; Black, Dennis; Cauley, Jane A; Cummings, Steven R; LeBlanc, Erin S; Laughlin, Gail A; Nielson, Carrie M; Broughton, Augusta; Kado, Deborah M; Hoffman, Andrew R; Jamal, Sophie A; Barrett-Connor, Elizabeth; Orwoll, Eric S

    2016-03-01

    The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463, including 1054 with follow-up data 4.6years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade≥2, N=140, 9.6%) and new or worsening vertebral fracture (change in SQ grade≥1, N=55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men. PMID:26778261

  12. Quantitative ultrasound does not identify patients with an inflammatory disease at risk of vertebral deformities

    PubMed Central

    Heijckmann, A Caroline; Dumitrescu, Bianca; Nieuwenhuijzen Kruseman, Arie C; Geusens, Piet; Wolffenbuttel, Bruce HR; De Vries, Jolanda; Drent, Marjolein; Huijberts, Maya SP

    2008-01-01

    Background Previous studies from our group have shown that a high prevalence of vertebral deformities suggestive of fracture can be found in patients with an inflammatory disease, despite a near normal bone mineral density (BMD). As quantitative ultrasound (QUS) of the heel can be used for refined assessment of bone strength, we evaluated whether QUS can be used to identify subjects with an inflammatory disease with an increased chance of having a vertebral fracture. Methods 246 patients (mean age: 44 ± 12.4 years) with an inflammatory disease (sarcoidosis or inflammatory bowel disease (IBD)) were studied. QUS of the heel and BMD of the hip (by dual X-ray absorptiometry (DXA)) were measured. Furthermore lateral single energy densitometry of the spine for assessment of vertebral deformities was done. Logistic regression analysis was performed to assess the strength of association between the prevalence of a vertebral deformity and BMD and QUS parameters, adjusted for gender and age. Results Vertebral deformities (ratio of <0.80) were found in 72 vertebrae of 54 subjects (22%). In contrast to the QUS parameters BUA (broadband ultrasound attenuation) and SOS (speed of sound), T-score of QUS and T-scores of the femoral neck and trochanter (DXA) were lower in the group of patients with vertebral deformities. Logistic regression analysis showed that the vertebral deformity risk increases by about 60 to 90% per 1 SD reduction of BMD (T-score) determined with DXA but not with QUS. Conclusion Our findings imply that QUS measurements of the calcaneus in patients with an inflammatory condition, such as sarcoidosis and IBD, are likely of limited value to identify patients with a vertebral fracture. PMID:18492278

  13. Problems with six-point vertebral morphometry

    NASA Astrophysics Data System (ADS)

    Gardner, Jill C.; Yaffe, Laurence G.; Johansen, Jennifer M.; von Ingersleben, Gabriel; Chestnut, Charles H., III

    1998-06-01

    In this study we have examined errors in measurements of vertebral heights and vertebral area resulting from spin rotation and projection effects in x-ray images. Measurement errors were evaluated with phantom images, and simulated rotations of a 3D spine model. An active contour model (snake) was used for measurements of vertebral area. The model contained two pressure parameters which were needed to obtain good fits of the snake to upper and lower edges (endplates) of rotated vertebral bodies. Details of the snake model are included in this report. The results of this study indicate that six point vertebral morphometry can result to significant measurement errors, representing an overestimation of vertebral height and area, in cases showing projection effects and concealed endplate contours. In serial studies, such errors could produce the erroneous appearance of `growing' vertebral bodies. One can improve the accuracy of the morphometric analysis by using additional fiducial points placed on corresponding endplate contours. Additional useful information on fracture and vertebral deformity can be obtained by accurately tracking edge contours, using an active contour model, or comparable techniques.

  14. [Vertebral changes in histiocytosis x (author's transl)].

    PubMed

    Greinacher, I; Gutjahr, P

    1978-06-01

    Manifestations of histiocytosis X in the vertebral column occurred in 3 of 15 children. Pathological alterations showed a marked variability. Especially a vertebra plana should be considered as eosinophilic granuloma, until another cause is proven. Bone scans were positive in all three cases. Even in most severe cases with vertebral destruction neurological abnormalities were absent. PMID:308238

  15. 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

  16. Clay Minerals

    SciTech Connect

    Mueller, Karl T.; Sanders, Rebecca L.; Washton, Nancy M.

    2014-03-14

    Clay minerals are important components of the environment and are involved or implicated in processes such as the uptake of pollutants and the release of nutrients and as potential platforms for a number of chemical reactions. Owing to their small particle sizes (typically, on the order of microns or smaller) and mixing with a variety of other minerals and soil components, advanced characterization methods are needed to study their structures, dynamics, and reactivities. In this article, we describe the use of solid-state NMR methods to characterize the structures and chemistries of clay minerals. Early one-pulse magic-angle spinning (MAS) NMR studies of 27Al and 29Si have now been enhanced and extended with new studies utilizing advanced methodologies (such as Multiple Quantum MAS) as well as studies of less-sensitive nuclei. In additional work, the issue of reactivity of clay minerals has been addressed, including studies of reactive surface area in the environment. Utilizations of NMR-sensitive nuclides within the clay minerals themselves, and in molecules that react with specific sites on the clay mineral surfaces, have aided in understanding the reactivity of these complex aluminosilicate systems.

  17. 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

  18. 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

  19. Discordance between Prevalent Vertebral Fracture and Vertebral Strength Estimated by the Finite Element Method Based on Quantitative Computed Tomography in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    2015-01-01

    Background Bone fragility is increased in patients with type 2 diabetes mellitus (T2DM), but a useful method to estimate bone fragility in T2DM patients is lacking because bone mineral density alone is not sufficient to assess the risk of fracture. This study investigated the association between prevalent vertebral fractures (VFs) and the vertebral strength index estimated by the quantitative computed tomography-based nonlinear finite element method (QCT-based nonlinear FEM) using multi-detector computed tomography (MDCT) for clinical practice use. Research Design and Methods A cross-sectional observational study was conducted on 54 postmenopausal women and 92 men over 50 years of age, all of whom had T2DM. The vertebral strength index was compared in patients with and without VFs confirmed by spinal radiographs. A standard FEM procedure was performed with the application of known parameters for the bone material properties obtained from nondiabetic subjects. Results A total of 20 women (37.0%) and 39 men (42.4%) with VFs were identified. The vertebral strength index was significantly higher in the men than in the women (P<0.01). Multiple regression analysis demonstrated that the vertebral strength index was significantly and positively correlated with the spinal bone mineral density (BMD) and inversely associated with age in both genders. There were no significant differences in the parameters, including the vertebral strength index, between patients with and without VFs. Logistic regression analysis adjusted for age, spine BMD, BMI, HbA1c, and duration of T2DM did not indicate a significant relationship between the vertebral strength index and the presence of VFs. Conclusion The vertebral strength index calculated by QCT-based nonlinear FEM using material property parameters obtained from nondiabetic subjects, whose risk of fracture is lower than that of T2DM patients, was not significantly associated with bone fragility in patients with T2DM. This discordance

  20. 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

  1. A Grhl2-dependent gene network controls trophoblast branching morphogenesis.

    PubMed

    Walentin, Katharina; Hinze, Christian; Werth, Max; Haase, Nadine; Varma, Saaket; Morell, Robert; Aue, Annekatrin; Pötschke, Elisabeth; Warburton, David; Qiu, Andong; Barasch, Jonathan; Purfürst, Bettina; Dieterich, Christoph; Popova, Elena; Bader, Michael; Dechend, Ralf; Staff, Anne Cathrine; Yurtdas, Zeliha Yesim; Kilic, Ergin; Schmidt-Ott, Kai M

    2015-03-15

    Healthy placental development is essential for reproductive success; failure of the feto-maternal interface results in pre-eclampsia and intrauterine growth retardation. We found that grainyhead-like 2 (GRHL2), a CP2-type transcription factor, is highly expressed in chorionic trophoblast cells, including basal chorionic trophoblast (BCT) cells located at the chorioallantoic interface in murine placentas. Placentas from Grhl2-deficient mouse embryos displayed defects in BCT cell polarity and basement membrane integrity at the chorioallantoic interface, as well as a severe disruption of labyrinth branching morphogenesis. Selective Grhl2 inactivation only in epiblast-derived cells rescued all placental defects but phenocopied intraembryonic defects observed in global Grhl2 deficiency, implying the importance of Grhl2 activity in trophectoderm-derived cells. ChIP-seq identified 5282 GRHL2 binding sites in placental tissue. By integrating these data with placental gene expression profiles, we identified direct and indirect Grhl2 targets and found a marked enrichment of GRHL2 binding adjacent to genes downregulated in Grhl2(-/-) placentas, which encoded known regulators of placental development and epithelial morphogenesis. These genes included that encoding the serine protease inhibitor Kunitz type 1 (Spint1), which regulates BCT cell integrity and labyrinth formation. In human placenta, we found that human orthologs of murine GRHL2 and its targets displayed co-regulation and were expressed in trophoblast cells in a similar domain as in mouse placenta. Our data indicate that a conserved Grhl2-coordinated gene network controls trophoblast branching morphogenesis, thereby facilitating development of the site of feto-maternal exchange. This might have implications for syndromes related to placental dysfunction. PMID:25758223

  2. Micrasterias cells as a model system for research on morphogenesis.

    PubMed Central

    Meindl, U

    1993-01-01

    Micrasterias species have been the subject of numerous experimental studies on cell shape formation in the last 40 years. Chemical and physical treatment during different developmental stages, as well as investigations of ultrastructure by means of various different preparation methods, have yielded information about some principles of morphogenesis in the symmetric, highly ornamented Micrasterias cell. The basic symmetry of a Micrasterias cell is determined prior to mitosis and is established without nuclear control thereafter. Normal cell development, however, may occur only under the conditions of continuous protein synthesis throughout the cell cycle. A prepattern for the later cell shape seems to be present at the plasma membrane at the early stages of septum formation. It is realized by a local, patterned distributed incorporation of cell wall material that is delivered by Golgi-produced vesicles. The areas where fusions take place between the primary wall material containing vesicles and the plasma membrane are defined by inward ionic currents that are carried at least in part by calcium. These areas develop into lobes during the following course of cell growth. Cell shaping in Micrasterias cells is thus mediated by both an enhanced extension of the cell wall and an additional incorporation of wall material in the areas of the lobes. Numerous studies have indicated that actin plays an important role in morphogenesis, whereas microtubules do not participate in this process but are involved mainly in nuclear migration. The present review shows that although a wealth of details concerning Micrasterias morphogenesis has already been elucidated, two main questions, i.e., the method of septum formation and the splitting of the lobes, remain to be answered. Images PMID:7687738

  3. Modulation of Morphogenesis by Egfr during Dorsal Closure in Drosophila

    PubMed Central

    Cormier, Olga; Cheng, David Chung-Pei; Reed, Bruce; Harden, Nicholas

    2013-01-01

    During Drosophila embryogenesis the process of dorsal closure (DC) results in continuity of the embryonic epidermis, and DC is well recognized as a model system for the analysis of epithelial morphogenesis as well as wound healing. During DC the flanking lateral epidermal sheets stretch, align, and fuse along the dorsal midline, thereby sealing a hole in the epidermis occupied by an extra-embryonic tissue known as the amnioserosa (AS). Successful DC requires the regulation of cell shape change via actomyosin contractility in both the epidermis and the AS, and this involves bidirectional communication between these two tissues. We previously demonstrated that transcriptional regulation of myosin from the zipper (zip) locus in both the epidermis and the AS involves the expression of Ack family tyrosine kinases in the AS in conjunction with Dpp secreted from the epidermis. A major function of Ack in other species, however, involves the negative regulation of Egfr. We have, therefore, asked what role Egfr might play in the regulation of DC. Our studies demonstrate that Egfr is required to negatively regulate epidermal expression of dpp during DC. Interestingly, we also find that Egfr signaling in the AS is required to repress zip expression in both the AS and the epidermis, and this may be generally restrictive to the progression of morphogenesis in these tissues. Consistent with this theme of restricting morphogenesis, it has previously been shown that programmed cell death of the AS is essential for proper DC, and we show that Egfr signaling also functions to inhibit or delay AS programmed cell death. Finally, we present evidence that Ack regulates zip expression by promoting the endocytosis of Egfr in the AS. We propose that the general role of Egfr signaling during DC is that of a braking mechanism on the overall progression of DC. PMID:23579691

  4. NPAS1 regulates branching morphogenesis in embryonic lung.

    PubMed

    Levesque, Bernadette M; Zhou, Shutang; Shan, Lin; Johnston, Pamela; Kong, Yanping; Degan, Simone; Sunday, Mary E

    2007-04-01

    Drosophila trachealess (Trl), master regulator of tracheogenesis, has no known functional mammalian homolog. We hypothesized that genes similar to trachealess regulate lung development. Quantitative (Q)RT-PCR and immunostaining were used to determine spatial and temporal patterns of npas1 gene expression in developing murine lung. Immunostaining for alpha-smooth muscle actin demonstrated myofibroblasts, and protein gene product (PGP)9.5 identified neuroendocrine cells. Branching morphogenesis of embryonic lung buds was analyzed in the presence of antisense or sense oligodeoxynucleotides (ODN). Microarray analyses were performed to screen for changes in gene expression in antisense-treated lungs. QRT-PCR was used to validate the altered expression of key genes identified on the microarrays. We demonstrate that npas1 is expressed in murine embryonic lung. npas1 mRNA peaks early at Embryonic Day (E)10.5-E11.5, then drops to low levels. Sequencing verifies the identity of npas1 transcripts in embryonic lung. NPAS1 immunostaining occurs in nuclei of parabronchial mesenchymal cells, especially at the tracheal bifurcation. Arnt, the murine homolog of Tango (the heterodimerization partner for Trl) is also expressed in developing lung but at constant levels. npas1- or arnt-antisense ODN inhibit lung branching morphogenesis, with altered myofibroblast development and increased pulmonary neuroendocrine cells. On microarrays, we identify > 50 known genes down-regulated by npas1-antisense, including multiple genes regulating cell migration and cell differentiation. QRT-PCR confirms significantly decreased expression of the neurogenic genes RBP-Jk and Tle, and three genes involved in muscle development: beta-ig-h3, claudin-11, and myocardin. Npas1 can regulate myofibroblast distribution, branching morphogenesis, and neuroendocrine cell differentiation in murine embryonic lung. PMID:17110583

  5. 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

  6. Morphogenesis and propagation of complex cracks induced by thermal shocks.

    PubMed

    Bourdin, Blaise; Marigo, Jean-Jacques; Maurini, Corrado; Sicsic, Paul

    2014-01-10

    We study the genesis and the selective propagation of complex crack networks induced by thermal shock or drying of brittle materials. We use a quasistatic gradient damage model to perform large-scale numerical simulations showing that the propagation of fully developed cracks follows Griffith criterion and depends only on the fracture toughness, while crack morphogenesis is driven by the material's internal length. Our numerical simulations feature networks of parallel cracks and selective arrest in two dimensions and hexagonal columnar joints in three dimensions, without any hypotheses on cracks geometry, and are in good agreement with available experimental results. PMID:24483901

  7. 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

  8. 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

  9. Coordinating nodule morphogenesis with rhizobial infection in legumes.

    PubMed

    Oldroyd, Giles E D; Downie, J Allan

    2008-01-01

    The formation of nitrogen-fixing nodules on legumes requires an integration of infection by rhizobia at the root epidermis and the initiation of cell division in the cortex, several cell layers away from the sites of infection. Several recent developments have added to our understanding of the signaling events in the epidermis associated with the perception of rhizobial nodulation factors and the role of plant hormones in the activation of cell division leading to nodule morphogenesis. This review focuses on the tissue-specific nature of the developmental processes associated with nodulation and the mechanisms by which these processes are coordinated during the formation of a nodule. PMID:18444906

  10. Morphogenesis of an extended phenotype: four-dimensional ant nest architecture.

    PubMed

    Minter, Nicholas J; Franks, Nigel R; Brown, Katharine A Robson

    2012-03-01

    Animals produce a variety of structures to modify their environments adaptively. Such structures represent extended phenotypes whose development is rarely studied. To begin to rectify this, we used micro-computed tomography (CT) scanning and time-series experiments to obtain the first high-resolution dataset on the four-dimensional growth of ant nests. We show that extrinsic features within the environment, such as the presence of planes between layers of sediment, influence the architecture of Lasius flavus nests, with ants excavating horizontal tunnels along such planes. Intrinsically, the dimensions of the tunnels are associated with individual colonies, the dynamics of excavation can be explained by negative feedback and the angular distribution of tunnels is probably a result of local competition among tunnels for miners. The architecture and dynamics of ant nest excavation therefore result from local interactions of ants with one another and templates inherent in the environment. The influence of the environment on the form of structures has been documented across both biotic and abiotic domains. Our study opens up the utility of CT scanning as a technique for observing the morphogenesis of such structures. PMID:21849386

  11. Morphogenesis of an extended phenotype: four-dimensional ant nest architecture

    PubMed Central

    Minter, Nicholas J.; Franks, Nigel R.; Robson Brown, Katharine A.

    2012-01-01

    Animals produce a variety of structures to modify their environments adaptively. Such structures represent extended phenotypes whose development is rarely studied. To begin to rectify this, we used micro-computed tomography (CT) scanning and time-series experiments to obtain the first high-resolution dataset on the four-dimensional growth of ant nests. We show that extrinsic features within the environment, such as the presence of planes between layers of sediment, influence the architecture of Lasius flavus nests, with ants excavating horizontal tunnels along such planes. Intrinsically, the dimensions of the tunnels are associated with individual colonies, the dynamics of excavation can be explained by negative feedback and the angular distribution of tunnels is probably a result of local competition among tunnels for miners. The architecture and dynamics of ant nest excavation therefore result from local interactions of ants with one another and templates inherent in the environment. The influence of the environment on the form of structures has been documented across both biotic and abiotic domains. Our study opens up the utility of CT scanning as a technique for observing the morphogenesis of such structures. PMID:21849386

  12. 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)

  13. 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

  14. Biomineralization: mineral formation by organisms

    NASA Astrophysics Data System (ADS)

    Addadi, Lia; Weiner, Steve

    2014-09-01

    Organisms form many different types of minerals, with diverse shapes and sizes. These minerals fulfill a variety of functions. Inspired by the late H A Lowenstam, Steve Weiner and Lia Addadi have addressed many questions that relate to the mechanisms by which biological organisms produce these mineral phases and how their structures relate to their functions. Addadi and Weiner have explored the manner in which macromolecules extracted from mineralized tissues can interact with some crystal planes and not others, how these macromolecules can be occluded inside the forming crystals residing preferentially on specific crystal planes, and how they can induce one polymorph of calcium carbonate and not another to nucleate. Addadi and Weiner have also identified a novel strategy used by the sea urchin to form its smooth and convoluted mineralized skeletal elements. The strategy involves the initial production by cells of a highly disordered mineral precursor phase in vesicles, and then the export of this so-called amorphous phase to the site of skeletal formation, where it crystallizes. This strategy is now known to be used by many different invertebrate phyla, as well as by vertebrates to build bones and teeth. One of the major current research aims of the Weiner--Addadi group is to understand the biomineralization pathways whereby ions are extracted from the environment, are transported and deposited inside cells within vesicles, how these disordered phases are then transferred to the site of skeletal formation, and finally how the so-called amorphous phase crystallizes. Biology has clearly evolved unique strategies for forming crystalline minerals. Despite more than 300 years of research in this field, many challenging questions still remain unanswered.

  15. Sex difference in the validity of vertebral deformities as an index of prevalent vertebral osteoporotic fractures: a population survey of older men and women.

    PubMed

    Leidig-Bruckner, G; Limberg, B; Felsenberg, D; Bruckner, T; Holder, S; Kather, A; Miksch, J; Wüster, C; Ziegler, R; Scheidt-Nave, C

    2000-01-01

    Morphometric methods have been developed for standardized assessment of vertebral deformities in clinical and epidemiologic studies of spinal osteoporosis. However, vertebral deformity may be caused by a variety of other conditions. To examine the validity of morphometrically assessed vertebral deformities as an index of osteoporotic vertebral fractures, we developed an algorithm for radiological differential classification (RDC) based on a combination of quantitative and qualitative assessment of lateral spinal radiographs. Radiographs were obtained in a population of 50- to 80-year-old German women (n = 283) and men (n = 297) surveyed in the context of the European Vertebral Osteoporosis Study (EVOS). Morphometric methods (Eastell 3 SD and 4 SD criteria, McCloskey) were validated against RDC and against bone mineral density (BMD) at the femur and the lumbar spine. According to RDC 36 persons (6.2%) had at least one osteoporotic vertebral fracture; among 516 (88.9%) nonosteoporotics 154 had severe spondylosis, 132 had other spinal disease and 219 had normal findings; 14 persons (2.4%) could not be unequivocally classified. The prevalence of morphometrically assessed vertebral deformities ranged from 7.3% to 19.2% in women and from 3.5% to 16.6% in men, depending on the stringency of the morphometric criteria. The agreement between RDC and morphometric methods was poor. In men, 62-86% of cases with vertebral deformities were classified as nonosteoporotic (severe spondylosis or other spinal disease) by RDC, compared with 31-68% in women. Among these, most had wedge deformities of the thoracic spine. On the other hand, up to 80% of osteoporotic vertebral fractures in men and up to 48% in women were missed by morphometry, in particular endplate fractures at the lumbar spine. In the group with osteoporotic vertebral fractures by RDC the proportion of persons with osteoporosis according to the WHO criteria (T-score < -2.5 SD) was 90.0% in women and 86.6% in men

  16. 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

  17. 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.

  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 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

  1. 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.

  2. 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.

  3. 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

  4. PARP6 is a Regulator of Hippocampal Dendritic Morphogenesis

    PubMed Central

    Huang, Jeffrey Y.; Wang, Kang; Vermehren-Schmaedick, Anke; Adelman, John P.; Cohen, Michael S.

    2016-01-01

    Mono-ADP-ribosylation (MARylation) of mammalian proteins was first described as a post-translational modification catalyzed by bacterial toxins. It is now known that endogenous MARylation occurs in mammalian cells and is catalyzed by 11 members of the poly-ADP-ribose polymerase (PARP) family of proteins (17 in humans). The physiological roles of these PARPs remain largely unknown. Here we demonstrate that PARP6, a neuronally enriched PARP that catalyzes MARylation, regulates hippocampal dendrite morphogenesis, a process that is critical for proper neural circuit formation during development. Knockdown of PARP6 significantly decreased dendritic complexity in embryonic rat hippocampal neurons in culture and in vivo. Expression of wild-type PARP6 increased dendritic complexity; conversely, expression of a catalytically inactive PARP6 mutant, or a cysteine-rich domain deletion mutant that has significantly reduced catalytic activity, decreased dendritic complexity. The identification of PARP6 as a regulator of dendrite morphogenesis supports a role for MARylation in neurons during development. PMID:26725726

  5. Importance of MAP Kinases during Protoperithecial Morphogenesis in Neurospora crassa

    PubMed Central

    Jeffree, Chris E.; Oborny, Radek; Boonyarungsrit, Patid; Read, Nick D.

    2012-01-01

    In order to produce multicellular structures filamentous fungi combine various morphogenetic programs that are fundamentally different from those used by plants and animals. The perithecium, the female sexual fruitbody of Neurospora crassa, differentiates from the vegetative mycelium in distinct morphological stages, and represents one of the more complex multicellular structures produced by fungi. In this study we defined the stages of protoperithecial morphogenesis in the N. crassa wild type in greater detail than has previously been described; compared protoperithecial morphogenesis in gene-deletion mutants of all nine mitogen-activated protein (MAP) kinases conserved in N. crassa; confirmed that all three MAP kinase cascades are required for sexual development; and showed that the three different cascades each have distinctly different functions during this process. However, only MAP kinases equivalent to the budding yeast pheromone response and cell wall integrity pathways, but not the osmoregulatory pathway, were essential for vegetative cell fusion. Evidence was obtained for MAP kinase signaling cascades performing roles in extracellular matrix deposition, hyphal adhesion, and envelopment during the construction of fertilizable protoperithecia. PMID:22900028

  6. A simple probabilistic model of submicroscopic diatom morphogenesis

    PubMed Central

    Willis, L.; Cox, E. J.; Duke, T.

    2013-01-01

    Unicellular algae called diatoms morph biomineral compounds into tough exoskeletons via complex intracellular processes about which there is much to be learned. These exoskeletons feature a rich variety of structures from submicroscale to milliscale, many that have not been reproduced in vitro. In order to help understand this complex miniature morphogenesis, here we introduce and analyse a simple model of biomineral kinetics, focusing on the exoskeleton's submicroscopic patterned planar structures called pore occlusions. The model reproduces most features of these pore occlusions by retuning just one parameter, thereby indicating what physio-biochemical mechanisms could sufficiently explain morphogenesis at the submicroscopic scale: it is sufficient to identify a mechanism of lateral negative feedback on the biomineral reaction kinetics. The model is nonlinear and stochastic; it is an extended version of the threshold voter model. Its mean-field equation provides a simple and, as far as the authors are aware, new way of mapping out the spatial patterns produced by lateral inhibition and variants thereof. PMID:23554345

  7. LKB1 and Notch Pathways Interact and Control Biliary Morphogenesis

    PubMed Central

    Just, Pierre-Alexandre; Poncy, Alexis; Charawi, Sara; Dahmani, Rajae; Traore, Massiré; Dumontet, Typhanie; Drouet, Valérie; Dumont, Florent; Gilgenkrantz, Hélène; Colnot, Sabine; Terris, Benoit; Coulouarn, Cédric; Lemaigre, Frédéric; Perret, Christine

    2015-01-01

    Background LKB1 is an evolutionary conserved kinase implicated in a wide range of cellular functions including inhibition of cell proliferation, regulation of cell polarity and metabolism. When Lkb1 is inactivated in the liver, glucose homeostasis is perturbed, cellular polarity is affected and cholestasis develops. Cholestasis occurs as a result from deficient bile duct development, yet how LKB1 impacts on biliary morphogenesis is unknown. Methodology/Principal Findings We characterized the phenotype of mice in which deletion of the Lkb1 gene has been specifically targeted to the hepatoblasts. Our results confirmed that lack of LKB1 in the liver results in bile duct paucity leading to cholestasis. Immunostaining analysis at a prenatal stage showed that LKB1 is not required for differentiation of hepatoblasts to cholangiocyte precursors but promotes maturation of the primitive ductal structures to mature bile ducts. This phenotype is similar to that obtained upon inactivation of Notch signaling in the liver. We tested the hypothesis of a functional overlap between the LKB1 and Notch pathways by gene expression profiling of livers deficient in Lkb1 or in the Notch mediator RbpJκ and identified a mutual cross-talk between LKB1 and Notch signaling. In vitro experiments confirmed that Notch activity was deficient upon LKB1 loss. Conclusion LKB1 and Notch share a common genetic program in the liver, and regulate bile duct morphogenesis. PMID:26689699

  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. PMID:26778757

  9. 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.

  10. 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

  11. 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

  12. AFR1 promotes polarized apical morphogenesis in Saccharomyces cerevisiae.

    PubMed Central

    Konopka, J B; DeMattei, C; Davis, C

    1995-01-01

    The G protein-coupled alpha-factor receptor promotes polarized growth toward a mating partner. alpha-Factor induces the expression of AFR1, which acts together with the receptor C terminus to promote normal morphogenesis. The function of AFR1 was investigated by engineering cells to constitutively express AFR1 without alpha-factor. Constitutive AFR1 expression caused cells to form elongated buds that demonstrate that AFR1 can also interact with the morphogenesis components that promote bud formation. A similar elongated bud phenotype is caused by mutation of the CDC3, CDC10, CDC11, and CDC12 genes, which encode putative filament proteins that form a ring at the bud neck. AFR1 may act directly on the filament proteins, since immunolocalization detected AFR1 at the bud neck and interaction of AFR1 and CDC12 was detected in the two-hybrid protein assay. AFR1 localized to the base of pheromone-induced projections. These results suggest that AFR1 and the putative filament proteins act together with the receptor to facilitate proper localization of components during mating. PMID:7823940

  13. 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

  14. 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

  15. Fungal quorum sensing molecules: Role in fungal morphogenesis and pathogenicity.

    PubMed

    Wongsuk, Thanwa; Pumeesat, Potjaman; Luplertlop, Natthanej

    2016-05-01

    When microorganisms live together in high numbers, they need to communicate with each other. To achieve cell-cell communication, microorganisms secrete molecules called quorum-sensing molecules (QSMs) that control their biological activities and behaviors. Fungi secrete QSMs such as farnesol, tyrosol, phenylethanol, and tryptophol. The role of QSMs in fungi has been widely studied in both yeasts and filamentous fungi, for example in Candida albicans, C. dubliniensis, Aspergillus niger, A. nidulans, and Fusarium graminearum. QSMs impact fungal morphogenesis (yeast-to-hypha formation) and also play a role in the germination of macroconidia. QSMs cause fungal cells to initiate programmed cell death, or apoptosis, and play a role in fungal pathogenicity. Several types of QSMs are produced during stages of biofilm development to control cell population or morphology in biofilm communities. This review article emphasizes the role of fungal QSMs, especially in fungal morphogenesis, biofilm formation, and pathogenicity. Information about QSMs may lead to improved measures for controlling fungal infection. PMID:26972663

  16. Industrial Minerals

    ERIC Educational Resources Information Center

    Bradbury, James C.

    1978-01-01

    The past year is seen as not particularly good for industrial minerals and for industry in general. Environmental concerns continued to trouble the industry with unacceptable asbestos concentrations and chlorofluorocarbon effects on ozone. A halting U.S. economy also affected industrial progress. (MA)

  17. Prevalent Vertebral Fractures among Children Initiating Glucocorticoid Therapy for the Treatment of Rheumatic Disorders

    PubMed Central

    Huber, A.M.; Gaboury, I.; Cabral, D.A.; Lang, B.; Ni, A.; Stephure, D.; Taback, S.; Dent, P.; Ellsworth, J.; LeBlanc, C.; Saint-Cyr, C.; Scuccimarri, R.; Hay, J.; Lentle, B.; Matzinger, M.; Shenouda, N.; Moher, D.; Rauch, F.; Siminoski, K.; Ward, L.M.

    2014-01-01

    Objectives Vertebral fractures are an under-recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid (GC) therapy. Methods Children were categorized as follows: juvenile dermatomyositis (juvenile DM, N=30), juvenile idiopathic arthritis (JIA; N=28), systemic lupus erythematosus (SLE) and related conditions (N=26), systemic arthritis (N=22), systemic vasculitis (N=16), and other conditions (N=12). Thoracolumbar spine radiograph and dual energy x-ray absorptiometry for lumbar spine areal bone mineral density (LS BMD) were performed within 30 days of GC initiation. Genant semi-quantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative GC dose, underlying diagnosis, LS BMD Z-score and back pain were analyzed for association with vertebral fracture. Results Thirteen vertebral fractures were noted in 9 children (7%). Six patients had a single vertebral fracture and three patients had two to three fractures. Fractures were clustered in the mid-thoracic region (69%). Three vertebral fractures (23%) were moderate (Grade 2); the others were mild (Grade 1). For the entire cohort, mean (±SD) LS BMD Z-score was significantly different from zero (−0.55±1.2, p<0.001) despite a mean height Z-score that was similar to the healthy average (0.02±1.0, p=0.825). Back pain was highly associated with increased odds for fracture (OR 10.6, 95% CI 2.1 to 53.8, p=0.004). Conclusions In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged GC exposure. PMID:20391507

  18. High prevalence of radiological vertebral fractures in adult patients with Ehlers-Danlos syndrome.

    PubMed

    Mazziotti, G; Dordoni, C; Doga, M; Galderisi, F; Venturini, M; Calzavara-Pinton, P; Maroldi, R; Giustina, A; Colombi, M

    2016-03-01

    Previous studies have reported an increased prevalence of osteoporosis in Ehlers–Danlos syndrome (EDS), but these were limited by a small number of patients and lack of information on fragility fractures. In this crosssectional study, we evaluated the prevalence of radiological vertebral fractures (by quantitative morphometry) and bone mineral density (BMD, at lumbar spine, total hip and femoral neck by dual-energy X-ray absorptiometry) in 52 consecutive patientswith EDS (10 males, 42 females; median age 41 years, range: 21–71; 12with EDS classic type, 37 with EDS hypermobility type, 1 with classic vascular-like EDS, and 2 without specific classification) and 197 control subjects (163 females and 34 males; median age 49 years, range: 26–83) attending an outpatient bone clinic. EDS patients were also evaluated for back pain by numeric pain rating scale (NRS- 11).Vertebral fractures were significantly more prevalent in EDS as compared to the control subjects (38.5% vs. 5.1%; p b 0.001) without significant differences in BMD at either skeletal sites. In EDS patients, the prevalence of vertebral fractures was not significantly (p = 0.72) different between classic and hypermobility types. BMD was not significantly different between fractured and non-fractured EDS patients either at lumbar spine (p = 0.14), total hip (p=0.08), or femoral neck (p=0.21). Severe back pain(≥7 NRS)was more frequent in EDS patients with vertebral fractures as compared to thosewithout fractures (60% vs. 28%; p=0.04). Inconclusion, this is the first study showing high prevalence of vertebral fractures in a relatively large population of EDS patients. Vertebral fractures were associated with more severe back pain suggesting a potential involvement of skeletal fragility in determining poor quality of life. The lack of correlation between vertebral fractures and BMD is consistent with the hypothesis that bone quality may be impaired in EDS. PMID:26708925

  19. A decision support scheme for vertebral geometry on body CT scans

    NASA Astrophysics Data System (ADS)

    Hayashi, Tatsuro; Chen, Huayue; Miyamoto, Kei; Zhou, Xiangrong; Hara, Takeshi; Yokoyama, Ryujiro; Kanematsu, Masayuki; Hoshi, Hiroaki; Fujita, Hiroshi

    2011-03-01

    For gaining a better understanding of bone quality, a great deal of attention has been paid to vertebral geometry in anatomy. The aim of this study was to design a decision support scheme for vertebral geometries. The proposed scheme consists of four parts: (1) automated extraction of bone, (2) generation of median plane image of spine, (3) detection of vertebrae, (4) quantification of vertebral body width, depth, cross-sectional area (CSA), and trabecular bone mineral density (BMD). The proposed scheme was applied to 10 CT cases and compared with manual tracking performed by an anatomy expert. Mean differences in the width, depth, CSA, and trabecular BMD were 3.1 mm, 1.4 mm, 88.7 mm2, and 7.3 mg/cm3, respectively. We found moderate or high correlations in vertebral geometry between our scheme and manual tracking (r > 0.72). In contrast, measurements obtained by using our scheme were slightly smaller than those acquired from manual tracking. However, the outputs of the proposed scheme in most CT cases were regarded to be appropriate on the basis of the subjective assessment of an anatomy expert. Therefore, if the appropriate outputs from the proposed scheme are selected in advance by an anatomy expert, the results can potentially be used for an analysis of vertebral body geometries.

  20. Vertebrate eye development as modeled in Drosophila.

    PubMed

    Wawersik, S; Maas, R L

    2000-04-12

    Pax6, a member of the paired-box family of transcription factors, is critical for oculogenesis in both vertebrates and insects. Identification of potential vertebrate Pax6 targets has been guided by studies in Drosophila, where the Pax6 homologs eyeless ( ey ) and twin of eyeless ( toy ) function within a network of genes that synergistically pattern the developing fly eye. These targets, which share homology with the fly genes sine oculis, eyes absent and dachshund, exist in mice and humans as the Six, Eya and Dach gene families. Members of these gene families are present in the developing vertebrate eye, and preliminary studies suggest that they may function in a network analogous to that in the fly. Thus, despite radically different architecture, a similar molecular scaffold underlies both vertebrate and fly eye patterning, suggesting that the considerable power of Drosophila genetics can be harnessed to study mammalian ocular development. PMID:10767315

  1. Evolution of Herbivory in Terrestrial Vertebrates

    NASA Astrophysics Data System (ADS)

    Sues, Hans-Dieter

    2000-08-01

    Although herbivory probably first appeared over 300 million years ago, it only became established as a common feeding strategy during Late Permian times. Subsequently, herbivory evolved in numerous lineages of terrestrial vertebrates, and the acquisition of this mode of feeding was frequently associated with considerable evolutionary diversification in those lineages. This book represents a comprehensive overview of the evolution of herbivory in land-dwelling amniote tetrapods in recent years. In Evolution of Herbivory in Terrestrial Vertebrates, leading experts review the evolutionary history and structural adaptations required for feeding on plants in the major groups of land-dwelling vertebrates, especially dinosaurs and ungulate mammals. As such, this volume will be the definitive reference source on this topic for evolutionary biologists and vertebrate paleontologists.

  2. 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

  3. 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

  4. Update of vertebral cementoplasty in porotic patients

    PubMed Central

    Masala, Salvatore; Muto, Mario

    2015-01-01

    Vertebroplasty (VP) is a percutaneous mini-invasive technique developed in the late 1980s as antalgic and stabilizing treatment in patients affected by symptomatic vertebral fracture due to porotic disease, traumatic injury and primary or secondary vertebral spine tumors. The technique consists of a simple metameric injection of an inert cement (poly-methyl-methacrylate, PMMA), through a needle by trans-peduncular, parapeduncular or trans-somatic approach obtaining a vertebral augmentation and stabilization effect associated with pain relief. The technique is simple and fast, and should be performed under fluoroscopy or CT guidance in order to obtain a good result with low complication rate. The aim of this paper is to illustrate the utility of VP, the indications-contraindications criteria, how to technically perform the technique using imaging guidance, and the results and complications of this treatment in patients affected by symptomatic vertebral compression fracture. PMID:26015527

  5. 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

  6. Innate immunity in vertebrates: an overview.

    PubMed

    Riera Romo, Mario; Pérez-Martínez, Dayana; Castillo Ferrer, Camila

    2016-06-01

    Innate immunity is a semi-specific and widely distributed form of immunity, which represents the first line of defence against pathogens. This type of immunity is critical to maintain homeostasis and prevent microbe invasion, eliminating a great variety of pathogens and contributing with the activation of the adaptive immune response. The components of innate immunity include physical and chemical barriers, humoral and cell-mediated components, which are present in all jawed vertebrates. The understanding of innate defence mechanisms in non-mammalian vertebrates is the key to comprehend the general picture of vertebrate innate immunity and its evolutionary history. This is also essential for the identification of new molecules with applications in immunopharmacology and immunotherapy. In this review, we describe and discuss the main elements of vertebrate innate immunity, presenting core findings in this field and identifying areas that need further investigation. PMID:26878338

  7. [Vertebral osteomyelitis associated with epidural block].

    PubMed

    Carrillo Esper, R; Cruz-Bautista, I

    2001-01-01

    Infectious complications after epidural anesthesia are infrequent and the most common are epidural and subdural abscess. We report one rare case of vertebral osteomyelitus associated with an epidural catheter and review the literature. PMID:11381807

  8. Recombination Drives Vertebrate Genome Contraction

    PubMed Central

    Nam, Kiwoong; Ellegren, Hans

    2012-01-01

    Selective and/or neutral processes may govern variation in DNA content and, ultimately, genome size. The observation in several organisms of a negative correlation between recombination rate and intron size could be compatible with a neutral model in which recombination is mutagenic for length changes. We used whole-genome data on small insertions and deletions within transposable elements from chicken and zebra finch to demonstrate clear links between recombination rate and a number of attributes of reduced DNA content. Recombination rate was negatively correlated with the length of introns, transposable elements, and intergenic spacer and with the rate of short insertions. Importantly, it was positively correlated with gene density, the rate of short deletions, the deletion bias, and the net change in sequence length. All these observations point at a pattern of more condensed genome structure in regions of high recombination. Based on the observed rates of small insertions and deletions and assuming that these rates are representative for the whole genome, we estimate that the genome of the most recent common ancestor of birds and lizards has lost nearly 20% of its DNA content up until the present. Expansion of transposable elements can counteract the effect of deletions in an equilibrium mutation model; however, since the activity of transposable elements has been low in the avian lineage, the deletion bias is likely to have had a significant effect on genome size evolution in dinosaurs and birds, contributing to the maintenance of a small genome. We also demonstrate that most of the observed correlations between recombination rate and genome contraction parameters are seen in the human genome, including for segregating indel polymorphisms. Our data are compatible with a neutral model in which recombination drives vertebrate genome size evolution and gives no direct support for a role of natural selection in this process. PMID:22570634

  9. Vertebral artery occlusion and oral contraceptives.

    PubMed Central

    Ask-Upmark, E; Bickerstaff, E R

    1976-01-01

    If vertebral artery occlusion occurs in degenerative arterial disease it is almost invariably left-sided, but in vertebral artery deficiency syndromes associated with oral contraceptives a striking preponderance of right-sided involvement has been shown. This observation adds support to the view that causes other than changes in the wall of the vessel at the site of occlusion must be sought as an explanation of the occlusion. PMID:1252812

  10. 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.

  11. 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

  12. Cilia in vertebrate development and disease

    PubMed Central

    Oh, Edwin C.; Katsanis, Nicholas

    2012-01-01

    Through the combined study of model organisms, cell biology, cell signaling and medical genetics we have significantly increased our understanding of the structure and functions of the vertebrate cilium. This ancient organelle has now emerged as a crucial component of certain signaling and sensory perception pathways in both developmental and homeostatic contexts. Here, we provide a snapshot of the structure, function and distribution of the vertebrate cilium and of the pathologies that are associated with its dysfunction. PMID:22223675

  13. Cervical vertebral fusion with anterior meningocele

    PubMed Central

    Chavredakis, Emmanuel; Carter, David; Bhojak, Manesh; Jenkinson, Michael D; Clark, Simon R

    2015-01-01

    We present the first described case of cervical vertebral fusion associated with anterior meningocele and syringomyelia. A 45-year-old woman presented with minor trauma, and plain cervical spine radiographs highlighted a congenital deformity of the cervical vertebral bodies. She had a normal neurological examination; however, further imaging revealed a meningocele and syringomyelia. This case highlights the importance of thorough imaging investigation when presented with a congenital deformity in order to detect and prevent development of degenerative spinal cord pathologies. PMID:25923673

  14. Risk factors for vertebral deformities in men: relationship to number of vertebral deformities. European Vertebral Osteoporosis Study Group.

    PubMed

    Ismail, A A; O'Neill, T W; Cooper, C; Silman, A J

    2000-02-01

    Recent epidemiological studies suggest a similar overall prevalence of vertebral deformity in men to that in women, though the influence of increasing age on the prevalence of vertebral deformity is less marked in men. However, most affected men have only a single or two vertebral deformities, which may be unrelated to osteoporosis. The aim of this study was to examine the role of risk factors, previously demonstrated to be associated with vertebral osteoporosis in females, in men with single/dual deformities compared to those with multiple deformities. Age stratified random samples of men aged 50 years and over were recruited from population registers in 30 European centers as part of the European Vertebral Osteoporosis Study (EVOS). Subjects had a lateral spinal radiograph and the presence of vertebral deformity was determined using the McCloskey algorithm. Lifestyle and other risk factor data were obtained from an interviewer-administered questionnaire. In all 6937 men with a mean age of 64.4 (SD = 8.5) years were studied of whom 738 (10.6%) subjects had one or two deformities, and 109 (1.6%) subjects had three or more deformities. There was a marked increase in the prevalence of multiple vertebral deformities with increasing age, but only a modest effect of age on the prevalence of single deformities. Associations between various risk factors for osteoporosis and vertebral deformity were analyzed separately in men with single/dual vertebral deformity from those with three or more deformities using logistic regression. After adjustment for age, there were statistically significant associations between the following risk factors and multiple deformities: previous hip fracture (odds ratio [OR] 10.5), lack of regular physical activity (OR 2.9), low body mass (OR 2.5), and previous steroid use (OR 2.3). By contrast, there were only weak associations with these same variables in males with single/dual deformities and, apart from poor self-reported general health, all

  15. Vertebral Strength and Estimated Fracture Risk Across the BMI Spectrum in Women.

    PubMed

    Bachmann, Katherine N; Bruno, Alexander G; Bredella, Miriam A; Schorr, Melanie; Lawson, Elizabeth A; Gill, Corey M; Singhal, Vibha; Meenaghan, Erinne; Gerweck, Anu V; Eddy, Kamryn T; Ebrahimi, Seda; Koman, Stuart L; Greenblatt, James M; Keane, Robert J; Weigel, Thomas; Dechant, Esther; Misra, Madhusmita; Klibanski, Anne; Bouxsein, Mary L; Miller, Karen K

    2016-02-01

    Somewhat paradoxically, fracture risk, which depends on applied loads and bone strength, is elevated in both anorexia nervosa and obesity at certain skeletal sites. Factor-of-risk (Φ), the ratio of applied load to bone strength, is a biomechanically based method to estimate fracture risk; theoretically, higher Φ reflects increased fracture risk. We estimated vertebral strength (linear combination of integral volumetric bone mineral density [Int.vBMD] and cross-sectional area from quantitative computed tomography [QCT]), vertebral compressive loads, and Φ at L4 in 176 women (65 anorexia nervosa, 45 lean controls, and 66 obese). Using biomechanical models, applied loads were estimated for: 1) standing; 2) arms flexed 90°, holding 5 kg in each hand (holding); 3) 45° trunk flexion, 5 kg in each hand (lifting); 4) 20° trunk right lateral bend, 10 kg in right hand (bending). We also investigated associations of Int.vBMD and vertebral strength with lean mass (from dual-energy X-ray absorptiometry [DXA]) and visceral adipose tissue (VAT, from QCT). Women with anorexia nervosa had lower, whereas obese women had similar, Int.vBMD and estimated vertebral strength compared with controls. Vertebral loads were highest in obesity and lowest in anorexia nervosa for standing, holding, and lifting (p < 0.0001) but were highest in anorexia nervosa for bending (p < 0.02). Obese women had highest Φ for standing and lifting, whereas women with anorexia nervosa had highest Φ for bending (p < 0.0001). Obese and anorexia nervosa subjects had higher Φ for holding than controls (p < 0.03). Int.vBMD and estimated vertebral strength were associated positively with lean mass (R = 0.28 to 0.45, p ≤ 0.0001) in all groups combined and negatively with VAT (R = -[0.36 to 0.38], p < 0.003) within the obese group. Therefore, women with anorexia nervosa had higher estimated vertebral fracture risk (Φ) for holding and bending because of inferior vertebral strength. Despite similar

  16. 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

  17. 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

  18. Mineral homeostasis and regulation of mineralization processes in the skeletons of sharks, rays and relatives (Elasmobranchii).

    PubMed

    Dean, Mason N; Ekstrom, Laura; Monsonego-Ornan, Efrat; Ballantyne, Jim; Witten, P Eckhard; Riley, Cyrena; Habraken, Wouter; Omelon, Sidney

    2015-10-01

    Sharks, rays and other elasmobranch fishes are characterized by a skeletal type that is unique among living vertebrates, comprised predominantly of an unmineralized cartilage, covered by a thin outer layer of sub-millimeter, mineralized tiles called tesserae. The mineralized portion of the skeleton appears to grow only by apposition, adding material at the edges of each tessera; maintenance of non-mineralized joints between tesserae is therefore vital, with precise control of mineral deposition and inhibition at the many thousands of growth fronts in the skeleton. Yet, we have only scattered evidence as to how the elasmobranchs mineralize and grow their skeletons. In this review, we take an "environment to skeleton" approach, drawing together research from a vast range of perspectives to track calcium and phosphate from the typical elasmobranch habitats into and through the body, to their deposition at tesseral growth fronts. In the process, we discuss the available evidence for skeletal resorption capability, mineral homeostasis hormones, and nucleation inhibition mechanisms. We also outline relevant theories in crystal nucleation and typical errors in measurements of serum calcium and phosphate in the study of vertebrate biology. We assemble research that suggests consensus in some concepts in elasmobranch skeletal development, but also highlight the very large gaps in our knowledge, particularly in regards to endocrine functional networks and biomineralization mechanisms. In this way, we lay out frameworks for future directions in the study of elasmobranch skeletal biology with stronger and more comparative links to research in other disciplines and into other taxa. PMID:26546857

  19. 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

  20. Mineral bioprocessing

    SciTech Connect

    Torma, A.E.

    1993-05-01

    In the last 25 years, the introduction of biotechnological methods in hydrometallurgy has created new opportunities and challenges for the mineral processing industry. This was especially true for the production of metal values from mining wastes and low-and-complex-grade mineral resources, which were considered economically not amenable for processing by conventional extraction methods. Using bio-assisted heap, dump and in-situ leaching technologies, copper and uranium extractions gained their first industrial applications. The precious metal industries were the next to adopt the bio-preoxidation technique in the extraction of gold from refractory sulfide-bearing ores and concentrates. A variety of other bioleaching opportunities exist for nickel, cobalt, cadmium and zinc sulfide leaching. Recently developed bioremediation methods and biosorption technologies have shown a good potential for industrial applications to remove trace heavy metal and radionuclide concentrations from contaminated soils, and mining and processing effluents.

  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. 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

  3. 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.

  4. 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

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

    PubMed

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

    2015-12-01

    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

  6. 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

  7. Elasticity-based targeted growth models of morphogenesis.

    PubMed

    Alford, Patrick W

    2015-01-01

    Embryonic tissue mechanics play an important role in regulating morphogenesis during organ formation, both in a bottom-up sense, where changes in gene expression drive mechanical shape changes, and in a top-down sense, where perturbations in tissue mechanics feed back to drive changes in gene expression. In growing tissues that can generate internal forces and have complex geometries, like those in the embryo, it can often be difficult to empirically determine the mechanical state of the tissue, let alone the relationships between gene expression and mechanical behavior. Mathematical models can be used to fill this gap. Here, we discuss elasticity-based models for growing tissues with a specific focus on targeted growth in embryonic tissues. PMID:25245704

  8. Quantitative, 3D Visualization of the Initiation and Progression of Vertebral Fractures Under Compression and Anterior Flexion.

    PubMed

    Jackman, Timothy M; Hussein, Amira I; Curtiss, Cameron; Fein, Paul M; Camp, Anderson; De Barros, Lidia; Morgan, Elise F

    2016-04-01

    clinical methods, such as algorithm-based qualitative (ABQ) assessment, that diagnose vertebral fracture on the basis of endplate depression. © 2015 American Society for Bone and Mineral Research. PMID:26590372

  9. Epithelial inactivation of Yy1 abrogates lung branching morphogenesis.

    PubMed

    Boucherat, Olivier; Landry-Truchon, Kim; Bérubé-Simard, Félix-Antoine; Houde, Nicolas; Beuret, Laurent; Lezmi, Guillaume; Foulkes, William D; Delacourt, Christophe; Charron, Jean; Jeannotte, Lucie

    2015-09-01

    Yin Yang 1 (YY1) is a multifunctional zinc-finger-containing transcription factor that plays crucial roles in numerous biological processes by selectively activating or repressing transcription, depending upon promoter contextual differences and specific protein interactions. In mice, Yy1 null mutants die early in gestation whereas Yy1 hypomorphs die at birth from lung defects. We studied how the epithelial-specific inactivation of Yy1 impacts on lung development. The Yy1 mutation in lung epithelium resulted in neonatal death due to respiratory failure. It impaired tracheal cartilage formation, altered cell differentiation, abrogated lung branching and caused airway dilation similar to that seen in human congenital cystic lung diseases. The cystic lung phenotype in Yy1 mutants can be partly explained by the reduced expression of Shh, a transcriptional target of YY1, in lung endoderm, and the subsequent derepression of mesenchymal Fgf10 expression. Accordingly, SHH supplementation partially rescued the lung phenotype in vitro. Analysis of human lung tissues revealed decreased YY1 expression in children with pleuropulmonary blastoma (PPB), a rare pediatric lung tumor arising during fetal development and associated with DICER1 mutations. No evidence for a potential genetic interplay between murine Dicer and Yy1 genes during lung morphogenesis was observed. However, the cystic lung phenotype resulting from the epithelial inactivation of Dicer function mimics the Yy1 lung malformations with similar changes in Shh and Fgf10 expression. Together, our data demonstrate the crucial requirement for YY1 in lung morphogenesis and identify Yy1 mutant mice as a potential model for studying the genetic basis of PPB. PMID:26329601

  10. 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

  11. A segmental pattern of alkaline phosphatase activity within the notochord coincides with the initial formation of the vertebral bodies

    PubMed Central

    Sindre, Grotmol; Kari, Nordvik; Harald, Kryvi; Geir, K Totland

    2005-01-01

    This study shows that segmental expression of alkaline phosphatase (ALP) activity by the notochord of the Atlantic salmon (Salmo salar L.) coincides with the initial mineralization of the vertebral body (chordacentrum), and precedes ALP expression by presumed somite-derived cells external to the notochordal sheath. The early expression of ALP indicates that the notochord plays an instructive role in the segmental patterning of the vertebral column. The chordacentra form segmentally as mineralized rings within the notochordal sheath, and ALP activity spreads within the chordoblast layer from ventral to dorsal, displaying the same progression and spatial distribution as the mineralization process. No ALP activity was observed in sclerotomal mesenchyme surrounding the notochordal sheath during initial formation of the chordacentra. Our results support previous findings indicating that the chordoblasts initiate a segmental differentiation of the notochordal sheath into chordacentra and intervertebral regions. PMID:15857363

  12. Vitamins and Minerals

    MedlinePlus

    ... I Help a Friend Who Cuts? Vitamins and Minerals KidsHealth > For Teens > Vitamins and Minerals Print A ... of a good thing? What Are Vitamins and Minerals? Vitamins and minerals make people's bodies work properly. ...

  13. 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.

  14. High prevalence of radiological vertebral fractures in women with prolactin-secreting pituitary adenomas.

    PubMed

    Mazziotti, Gherardo; Mancini, Tatiana; Mormando, Marilda; De Menis, Ernesto; Bianchi, Antonio; Doga, Mauro; Porcelli, Teresa; Vescovi, Pier Paolo; De Marinis, Laura; Giustina, Andrea

    2011-12-01

    Hyperprolactinemia may cause bone loss but data on fractures are scanty. The aim of this study was to evaluate the prevalence of vertebral fractures in women with prolactin (PRL)-secreting adenoma. In this cross-sectional study, 78 women (median age 45.5 years, range: 20-81) with PRL-secreting pituitary adenoma (66 with microadenoma and 12 with macroadenoma) and 156 control subjects, 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 25 patients with PRL-secreting adenoma (32.6%) and in 20 controls (12.8%, P < 0.001). Fractured patients were significantly older (P < 0.001) and had lower BMD T-score (P < 0.001), longer duration of disease (P < 0.001), higher serum PRL (P = 0.004) and lower serum IGF-I (P < 0.001) values as compared to patients who did not fracture. The prevalence of vertebral fractures was significantly (P < 0.001) higher in post-menopausal women with PRL-secreting adenoma as compared to pre-menopausal patients. Fractures occurred more frequently (P = 0.01) in patients with untreated hyperprolactinemia versus patients treated with cabergoline. Logistic regression analysis demonstrated that duration of disease maintained a significant correlation with vertebral fractures (odds ratio 1.16, C.I. 95% 1.02-1.33) even after correction for age, menopausal status, treatment with cabergoline, BMD, serum IGF-I and serum PRL values. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in women with PRL-secreting adenoma. PMID:21301967

  15. DXA parameters: beyond bone mineral density.

    PubMed

    Briot, Karine

    2013-05-01

    Dual-energy X-ray absorptiometry (DXA) is the reference standard for measuring bone mineral density (BMD) to diagnose osteoporosis. However, BMD measurement alone does not reliably predict the fracture risk. DXA can be used to assess other parameters (e.g. presence of vertebral fractures, bone microarchitecture, bone geometry, and body composition) simultaneously with BMD measurements, to help identify individuals at high fracture risk. Among these parameters, some are suitable for use in clinical practice, whereas others are reserved for research. Vertebral fracture assessment (VFA) is a very low radiation-dose method for detecting thoracic and lumbar vertebral fractures. Compared to standard radiography, VFA can be used in a broader population to detect asymptomatic vertebral fractures. The very good negative predictive value of VFA leads, in one-third of cases, to changes in patient management (drug treatment and prescription of radiographs). The trabecular bone score (TBS) is a noninvasively measured texture parameter that correlates with 3D bone microarchitecture parameters independently from BMD and that can be determined from lumbar-spine DXA images. Several cross-sectional studies and a prospective study established that the TBS was effective in identifying individuals with fractures. Additional studies will have to be performed to determine whether TBS determination can be recommended for everyday practice when treatment decisions are difficult. PMID:23622733

  16. 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

  17. [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. PMID:17762824

  18. 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

  19. 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

  20. Determinants of Microdamage in Elderly Human Vertebral Trabecular Bone

    PubMed Central

    Follet, Hélène; Farlay, Delphine; Bala, Yohann; Viguet-Carrin, Stéphanie; Gineyts, Evelyne; Burt-Pichat, Brigitte; Wegrzyn, Julien; Delmas, Pierre; Boivin, Georges; Chapurlat, Roland

    2013-01-01

    Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53) from donors 54–95 years of age (22 men and 30 women, 1 unknown) and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen) was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types. PMID:23457465

  1. Vertebral Adaptations to Large Body Size in Theropod Dinosaurs

    PubMed Central

    Wilson, John P.; Woodruff, D. Cary; Gardner, Jacob D.; Flora, Holley M.; Horner, John R.; Organ, Chris L.

    2016-01-01

    Rugose projections on the anterior and posterior aspects of vertebral neural spines appear throughout Amniota and result from the mineralization of the supraspinous and interspinous ligaments via metaplasia, the process of permanent tissue-type transformation. In mammals, this metaplasia is generally pathological or stress induced, but is a normal part of development in some clades of birds. Such structures, though phylogenetically sporadic, appear throughout the fossil record of non-avian theropod dinosaurs, yet their physiological and adaptive significance has remained unexamined. Here we show novel histologic and phylogenetic evidence that neural spine projections were a physiological response to biomechanical stress in large-bodied theropod species. Metaplastic projections also appear to vary between immature and mature individuals of the same species, with immature animals either lacking them or exhibiting smaller projections, supporting the hypothesis that these structures develop through ontogeny as a result of increasing bending stress subjected to the spinal column. Metaplastic mineralization of spinal ligaments would likely affect the flexibility of the spinal column, increasing passive support for body weight. A stiff spinal column would also provide biomechanical support for the primary hip flexors and, therefore, may have played a role in locomotor efficiency and mobility in large-bodied species. This new association of interspinal ligament metaplasia in Theropoda with large body size contributes additional insight to our understanding of the diverse biomechanical coping mechanisms developed throughout Dinosauria, and stresses the significance of phylogenetic methods when testing for biological trends, evolutionary or not. PMID:27442509

  2. Determinants of microdamage in elderly human vertebral trabecular bone.

    PubMed

    Follet, Hélène; Farlay, Delphine; Bala, Yohann; Viguet-Carrin, Stéphanie; Gineyts, Evelyne; Burt-Pichat, Brigitte; Wegrzyn, Julien; Delmas, Pierre; Boivin, Georges; Chapurlat, Roland

    2013-01-01

    Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53) from donors 54-95 years of age (22 men and 30 women, 1 unknown) and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen) was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types. PMID:23457465

  3. Vertebral Adaptations to Large Body Size in Theropod Dinosaurs.

    PubMed

    Wilson, John P; Woodruff, D Cary; Gardner, Jacob D; Flora, Holley M; Horner, John R; Organ, Chris L

    2016-01-01

    Rugose projections on the anterior and posterior aspects of vertebral neural spines appear throughout Amniota and result from the mineralization of the supraspinous and interspinous ligaments via metaplasia, the process of permanent tissue-type transformation. In mammals, this metaplasia is generally pathological or stress induced, but is a normal part of development in some clades of birds. Such structures, though phylogenetically sporadic, appear throughout the fossil record of non-avian theropod dinosaurs, yet their physiological and adaptive significance has remained unexamined. Here we show novel histologic and phylogenetic evidence that neural spine projections were a physiological response to biomechanical stress in large-bodied theropod species. Metaplastic projections also appear to vary between immature and mature individuals of the same species, with immature animals either lacking them or exhibiting smaller projections, supporting the hypothesis that these structures develop through ontogeny as a result of increasing bending stress subjected to the spinal column. Metaplastic mineralization of spinal ligaments would likely affect the flexibility of the spinal column, increasing passive support for body weight. A stiff spinal column would also provide biomechanical support for the primary hip flexors and, therefore, may have played a role in locomotor efficiency and mobility in large-bodied species. This new association of interspinal ligament metaplasia in Theropoda with large body size contributes additional insight to our understanding of the diverse biomechanical coping mechanisms developed throughout Dinosauria, and stresses the significance of phylogenetic methods when testing for biological trends, evolutionary or not. PMID:27442509

  4. Effect of an experimental oil spill on vertebral bone tissue quality in European sea bass (Dicentrarchus labrax L.).

    PubMed

    Danion, Morgane; Deschamps, Marie-Hélène; Thomas-Guyon, Hélène; Bado-Nilles, Anne; Le Floch, Stéphane; Quentel, Claire; Sire, Jean-Yves

    2011-10-01

    In order to identify biomarkers of oil pollution in fish we tested the effects of an experimental Light Cycle Oil (LCO) exposure on vertebral bone of sea bass, Dicentrarchus labrax L. A total of 60 adult fish were acclimated for fifteen days, then twenty were collected as controls (Day 0) while 40 were exposed to a soluble fraction of LCO (1136 ng L(-1) of ten Polycyclic Aromatic Hydrocarbons, PAHs) for seven days. Twenty of them were sampled at the end of the exposure period and the twenty last after a recovery period of fourteen days in clean seawater. Vertebral abnormalities were counted and bone mineralization, total bone area and bone density profiles were established for several post-cranial and caudal vertebrae. In sea bass, seven days of LCO exposure did not affect the frequency and severity of the vertebral abnormalities. No significant differences were observed in bone density and bone repartition (parameters of bone area profiles) between unexposed (Day 0), exposed (D7) and decontaminated (D21) fish. In contrast, bone mineralization of the vertebrae decreased in contaminated sea bass, but in a reversible way, which confirms a previous study in trout showing that this parameter is an early stress indicator. Our results suggest that vertebral bone mineralization could be used as a biomarker of PAH pollution in sea bass. It would be interesting to check this new biomarker in other teleost species exposed to various xenobiotics. PMID:21831432

  5. The evolution of early vertebrate photoreceptors

    PubMed Central

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

    2009-01-01

    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. PMID:19720654

  6. Pediatric congenital vertebral artery arteriovenous malformation.

    PubMed

    Shownkeen, Harish; Bova, Davide; Chenelle, Andrew G; Origitano, Thomas C

    2003-05-01

    Vertebral arteriovenous fistulas are rare in children and the congenital form has been seldom reported in the literature. Prior to using endovascular therapy techniques, only surgery was the main treatment. The most common endovascular treatment is through the use of detachable balloons. This report describes the clinical and radiological findings of a congenital vertebral artery fistula in a 20-month-old child. Balloons could not be safely employed; therefore, embolization was performed with Guglielmi detachable microcoils. We review the history and treatment of these lesions, their clinical presentation, and imaging features, including their outcome, with particular attention to the pediatric population. PMID:12695869

  7. Percutaneous vertebral augmentation for painful osteolytic vertebral metastasis: a case report

    PubMed Central

    Anselmetti, Giovanni C; Tutton, Sean M; Facchini, Francis R; Miller, Larry E; Block, Jon E

    2012-01-01

    Introduction Vertebral metastases are associated with significant pain, disability, and morbidity. Open surgery for fracture stabilization is often inappropriate in this population due to a poor risk-benefit profile, particularly if life expectancy is short. Percutaneous vertebroplasty and kyphoplasty are appealing adjunctive procedures in patients with malignancy for alleviation of intractable pain. However, these patients have higher risk of serious complications, notably cement extravasation. Described in this report is a case of a painful osteolytic vertebral metastasis that was successfully treated by a novel percutaneous vertebral augmentation system. Case presentation A 42-year-old Caucasian female presented with a history of metastatic lung cancer unresponsive to radiation and chemotherapy with symptoms inadequately controlled by opiates over the previous 6 months. Magnetic resonance imaging and spiral computed tomography with two-dimensional reconstruction showed an osteolytic vertebral metastasis with complete involvement of the T10 vertebral body, extending to the cortical vertebral wall anteriorly and posteriorly. The patient was treated with percutaneous vertebral augmentation (Kiva® VCF Treatment System, Benvenue Medical, Inc, Santa Clara, CA) utilizing a novel coil-shaped polyetheretherketone implant designed to minimize the risk of cement extravasation. After the minimally invasive procedure, bone cement distribution within the vertebral body was ideal, with no observed cement extravasation. No complications were reported, pain completely resolved within 24 hours, and use of intravenous narcotics was progressively diminished within 1 week. Complete pain relief was maintained throughout 4 months of follow-up. Conclusion The Kiva System represents a novel and effective minimally invasive treatment option for patients suffering from severe pain due to osteolytic vertebral metastasis. PMID:23754917

  8. Bone-density-specific fracture risk: A population-based study of the relationship between osteoporosis and vertebral fractures

    SciTech Connect

    Melton, L.J.; Wahner, H.W.; Richelson, L.S.; O'Fallon, W.M.; Dunn, W.L.; Riggs, B.L.

    1985-05-01

    The search for a specific level of bone density that clearly distinguishes patients with osteoporosis from those without has been largely unsuccessful. A different, ''gradient of risk'' model was used to assess the effect of various degrees of osteoporosis on the prevalence of vertebral fractures. The authors measured spinal (L/sub 1/-L/sub 4/) bone mineral (BM) with dual photon absorptiometry in an age-stratified random sample of Rochester, Minnesota women greater than or equal to 35 years old to estimate the distribution of spinal BM in the population of adult woman. The authors also assessed BM among women in the sample who had one or more vertebral fractures to estimate both the total number of women with vertebral fractures in the population and the distribution of spinal BM in such women. These population-based estimates were then used to calculate the prevalence rate of vertebral fracture at various levels of spinal BM. Women with spinal BM greater than or equal to 1.40 g/cm/sup 2/ were free of vertebral fractures. Among women with BM between 1.00 and 1.39 g/cm/sup 2/, the prevalence of vertebral fractures was about 7%. The prevalence rate increased as spinal BM decreased further. Among women with spinal BM<0.60 g/cm/sup 2/, all had at least one vertebral fracture (prevalence=100%). These data indicate that osteoporosis is a necessary cause of age-related vertebral fractures and, at certain low levels, is a sufficient cause of such fractures in conjunction with the activities of daily living.

  9. 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

  10. 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.

  11. Vertebral osteomyelitis combined streptococcal viridans endocarditis.

    PubMed

    Lee, Kuo-Chen; Tsai, Yi-Ting; Lin, Chih-Yuan; Tsai, Chien-Sung

    2003-01-01

    Endocarditis may be difficult to diagnose in patients with osteomyelitis in an early stage because they usually are treated for fever, bone pain and stiffness in the outpatient department. Herein we report an uncommon patient who developed severe lower back pain sustained for 2 months, and streptococcal viridans infected vertebral osteomyelitis combined endocarditis were diagnosed and cured. PMID:12493523

  12. Did Language Evolve Like the Vertebrate Eye?

    ERIC Educational Resources Information Center

    Botha, Rudolf P.

    2002-01-01

    Offers a critical appraisal of the way in which the idea that human language or some of its features evolved like the vertebrate eye by natural selection is articulated in Pinker and Bloom's (1990) selectionist account of language evolution. Argues that this account is less than insightful because it fails to draw some of the conceptual…

  13. Vertebral Osteomyelitis Caused by Helicobacter cinaedi

    PubMed Central

    Yoshizaki, Aisa; Takegawa, Hiroshi; Doi, Asako; Mizuno, Yasushi

    2015-01-01

    Helicobacter cinaedi causes bacteremia, cellulitis, and gastroenteritis. We report the first case of vertebral osteomyelitis caused by H. cinaedi in an elderly man with low back pain and fever. The pathogen was detected in blood and lumbar disc, and the infection was successfully treated with oral doxycycline for 11 weeks. PMID:26109448

  14. 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

  15. 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

  16. 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…

  17. A differential staining technique for vertebrate histology.

    PubMed

    Bhattacharyya, T K

    1979-03-01

    A staining method is described for studying micro-anatomy of different vertebrate tissues in the light microscope. A staining sequence of celestin blue--erythrosin--orange G--fast green with mordanting in phosphomolybdic acid yields a satisfactory differentiation and fine colour contrast in various tissues. The efficacy of the method was tested on different avian and mammalian tissues. PMID:86938

  18. 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.…

  19. 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

  20. microRNA Processing Pathway Regulates Olfactory Neuron Morphogenesis

    PubMed Central

    Berdnik, Daniela; Fan, Audrey P.; Potter, Christopher J.; Luo, Liqun

    2008-01-01

    Summary The micro(mi)RNA processing pathway produces miRNAs as posttranscriptional regulators of gene expression. The nuclear RNase III Drosha catalyzes the first processing step together with the dsRNA binding protein DGCR8/Pasha generating pre-miRNAs [1, 2]. The next cleavage employs the cytoplasmic RNase III Dicer producing miRNA duplexes [3, 4]. Finally, Argonautes are recruited with miRNAs into an RNA-induced silencing complex for mRNA recognition (Figure 1A). Here, we identify two members of the miRNA pathway, Pasha and Dicer-1, in a forward genetic screen for mutations that disrupt wiring specificity of Drosophila olfactory projection neurons (PNs). The olfactory system is built as discrete map of highly stereotyped neuronal connections [5, 6]. Each PN targets dendrites to a specific glomerulus in the antennal lobe and projects axons stereotypically into higher brain centers [7–9]. In selected PN classes, pasha and Dicer-1 mutants cause specific PN dendrite mistargeting in the antennal lobe and altered axonal terminations in higher brain centers. Furthermore, Pasha and Dicer-1 act cell-autonomously in postmitotic neurons to regulate dendrite and axon targeting during development. However, Argonaute-1 and Argonaute-2 are dispensable for PN morphogenesis. Our findings suggest a role for the miRNA processing pathway in establishing wiring specificity in the nervous system. PMID:19013069

  1. MicroRNA processing pathway regulates olfactory neuron morphogenesis.

    PubMed

    Berdnik, Daniela; Fan, Audrey P; Potter, Christopher J; Luo, Liqun

    2008-11-25

    The microRNA (miRNA) processing pathway produces miRNAs as posttranscriptional regulators of gene expression. The nuclear RNase III Drosha catalyzes the first processing step together with the dsRNA binding protein DGCR8/Pasha generating pre-miRNAs [1, 2]. The next cleavage employs the cytoplasmic RNase III Dicer producing miRNA duplexes [3, 4]. Finally, Argonautes are recruited with miRNAs into an RNA-induced silencing complex for mRNA recognition (Figure 1A). Here, we identify two members of the miRNA pathway, Pasha and Dicer-1, in a forward genetic screen for mutations that disrupt wiring specificity of Drosophila olfactory projection neurons (PNs). The olfactory system is built as discrete map of highly stereotyped neuronal connections [5, 6]. Each PN targets dendrites to a specific glomerulus in the antennal lobe and projects axons stereotypically into higher brain centers [7-9]. In selected PN classes, pasha and Dicer-1 mutants cause specific PN dendrite mistargeting in the antennal lobe and altered axonal terminations in higher brain centers. Furthermore, Pasha and Dicer-1 act cell autonomously in postmitotic neurons to regulate dendrite and axon targeting during development. However, Argonaute-1 and Argonaute-2 are dispensable for PN morphogenesis. Our findings suggest a role for the miRNA processing pathway in establishing wiring specificity in the nervous system. PMID:19013069

  2. The role of initial cells in maize anther morphogenesis.

    PubMed

    Dawe, R K; Freeling, M

    1992-12-01

    The near absence of cell movement in plants makes clonal analysis a particularly informative method for reconstructing the early events of organ formation. We traced the patterns of cell division during maize anther development by inducing sector boundaries that preceded the earliest events of anther initiation. In doing this, we were able to estimate the smallest number of cells that are fated to form an anther, characteristic cell division patterns that occur during anther morphogenesis, and the relationship between the pre-existing symmetry of the initial cells and the final symmetry of the mature anther. Four general conclusions are made: (1) anthers are initiated from small groups of 12 or fewer cells in each of two floral meristematic layers; (2) the early growth of the anther is more like a shoot than a glume or leaf; (3) cell ancestry does not dictate basic structure and (4) the orientation of initial cells predicts the orientation of the four pollen-containing microsporangia, which define the axes of symmetry on the mature anther. The final point is discussed with other data, and an explanation involving a 'structural template' is invoked. The idea is that the orientation of initial cells within the floral meristem establishes an architectural pattern into which anther cells are recruited without regard to their cellular lineages. The structural template hypothesis may prove to be generally applicable to problems of pattern formation in plants. PMID:1295730

  3. Endometrial Expression of Steroidogenic Factor 1 Promotes Cystic Glandular Morphogenesis.

    PubMed

    Vasquez, Yasmin M; Wu, San-Pin; Anderson, Matthew L; Hawkins, Shannon M; Creighton, Chad J; Ray, Madhumita; Tsai, Sophia Y; Tsai, Ming-Jer; Lydon, John P; DeMayo, Francesco J

    2016-05-01

    Epigenetic silencing of steroidogenic factor 1 (SF1) is lost in endometriosis, potentially contributing to de novo local steroidogenesis favoring inflammation and growth of ectopic endometrial tissue. In this study, we examine the impact of SF1 expression in the eutopic uterus by a novel mouse model that conditionally expresses SF1 in endometrium. In vivo SF1 expression promoted the development of enlarged endometrial glands and attenuated estrogen and progesterone responsiveness. Endometriosis induction by autotransplantation of uterine tissue to the mesenteric membrane resulted in the increase in size of ectopic lesions from SF1-expressing mice. By integrating the SF1-dependent transcriptome with the whole genome binding profile of SF1, we identified uterine-specific SF1-regulated genes involved in Wingless and Progesterone receptor-Hedgehog-Chicken ovalbumin upstream promoter transcription factor II signaling for gland development and epithelium-stroma interaction, respectively. The present results indicate that SF1 directly contributes to the abnormal uterine gland morphogenesis, an inhibition of steroid hormone signaling and activation of an immune response, in addition to previously postulated estrogen production. PMID:27018534

  4. A Monitor for Bud Emergence in the Yeast Morphogenesis Checkpoint

    PubMed Central

    Theesfeld, Chandra L.; Zyla, Trevin R.; Bardes, Elaine G.S.; Lew, Daniel J.

    2003-01-01

    Cell cycle transitions are subject to regulation by both external signals and internal checkpoints that monitor satisfactory progression of key cell cycle events. In budding yeast, the morphogenesis checkpoint arrests the cell cycle in response to perturbations that affect the actin cytoskeleton and bud formation. Herein, we identify a step in this checkpoint pathway that seems to be directly responsive to bud emergence. Activation of the kinase Hsl1p is dependent upon its recruitment to a cortical domain organized by the septins, a family of conserved filament-forming proteins. Under conditions that delayed or blocked bud emergence, Hsl1p recruitment to the septin cortex still took place, but hyperphosphorylation of Hsl1p and recruitment of the Hsl1p-binding protein Hsl7p to the septin cortex only occurred after bud emergence. At this time, the septin cortex spread to form a collar between mother and bud, and Hsl1p and Hsl7p were restricted to the bud side of the septin collar. We discuss models for translating cellular geometry (in this case, the emergence of a bud) into biochemical signals regulating cell proliferation. PMID:12925763

  5. Control of Swe1p degradation by the morphogenesis checkpoint.

    PubMed Central

    Sia, R A; Bardes, E S; Lew, D J

    1998-01-01

    In the budding yeast Saccharomyces cerevisiae, a cell cycle checkpoint coordinates mitosis with bud formation. Perturbations that transiently depolarize the actin cytoskeleton cause delays in bud formation, and a 'morphogenesis checkpoint' detects the actin perturbation and imposes a G2 delay through inhibition of the cyclin-dependent kinase, Cdc28p. The tyrosine kinase Swe1p, homologous to wee1 in fission yeast, is required for the checkpoint-mediated G2 delay. In this report, we show that Swe1p stability is regulated both during the normal cell cycle and in response to the checkpoint. Swe1p is stable during G1 and accumulates to a peak at the end of S phase or in early G2, when it becomes unstable and is degraded rapidly. Destabilization of Swe1p in G2 and M phase depends on the activity of Cdc28p in complexes with B-type cyclins. Several different perturbations of actin organization all prevent Swe1p degradation, leading to the persistence or further accumulation of Swe1p, and cell cycle delay in G2. PMID:9822611

  6. Sox17 is required for normal pulmonary vascular morphogenesis

    PubMed Central

    Lange, Alexander W.; Haitchi, Hans Michael; LeCras, Timothy D.; Sridharan, Anusha; Xu, Yan; Wert, Susan E.; James, Jeanne; Udell, Nicholas; Thurner, Philipp J.; Whitsett, Jeffrey A.

    2015-01-01

    The SRY-box containing transcription factor Sox17 is required for endoderm formation and vascular morphogenesis during embryonic development. In the lung, Sox17 is expressed in mesenchymal progenitors of the embryonic pulmonary vasculature and is restricted to vascular endothelial cells in the mature lung. Conditional deletion of Sox17 in splanchnic mesenchyme-derivatives using Dermo1-Cre resulted in substantial loss of Sox17 from developing pulmonary vascular endothelial cells and caused pulmonary vascular abnormalities before birth, including pulmonary vein varices, enlarged arteries, and decreased perfusion of the microvasculature. While survival of Dermo1-Cre;Sox17Δ/Δ mice (herein termed Sox17Δ/Δ) was unaffected at E18.5, most Sox17Δ/Δ mice died by 3 weeks of age. After birth, the density of the pulmonary microvasculature was decreased in association with alveolar simplification, biventricular cardiac hypertrophy, and valvular regurgitation. The severity of the postnatal cardiac phenotype was correlated with the severity of pulmonary vasculature abnormalities. Sox17 is required for normal formation of the pulmonary vasculature and postnatal cardiovascular homeostasis. PMID:24418654

  7. Sox17 is required for normal pulmonary vascular morphogenesis.

    PubMed

    Lange, Alexander W; Haitchi, Hans Michael; LeCras, Timothy D; Sridharan, Anusha; Xu, Yan; Wert, Susan E; James, Jeanne; Udell, Nicholas; Thurner, Philipp J; Whitsett, Jeffrey A

    2014-03-01

    The SRY-box containing transcription factor Sox17 is required for endoderm formation and vascular morphogenesis during embryonic development. In the lung, Sox17 is expressed in mesenchymal progenitors of the embryonic pulmonary vasculature and is restricted to vascular endothelial cells in the mature lung. Conditional deletion of Sox17 in splanchnic mesenchyme-derivatives using Dermo1-Cre resulted in substantial loss of Sox17 from developing pulmonary vascular endothelial cells and caused pulmonary vascular abnormalities before birth, including pulmonary vein varices, enlarged arteries, and decreased perfusion of the microvasculature. While survival of Dermo1-Cre;Sox17Δ/Δ mice (herein termed Sox17Δ/Δ) was unaffected at E18.5, most Sox17Δ/Δ mice died by 3 weeks of age. After birth, the density of the pulmonary microvasculature was decreased in association with alveolar simplification, biventricular cardiac hypertrophy, and valvular regurgitation. The severity of the postnatal cardiac phenotype was correlated with the severity of pulmonary vasculature abnormalities. Sox17 is required for normal formation of the pulmonary vasculature and postnatal cardiovascular homeostasis. PMID:24418654

  8. 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.

  9. Embryonic Heart Morphogenesis from Confocal Microscopy Imaging and Automatic Segmentation

    PubMed Central

    Gribble, Megan; Pertsov, Arkady M.; Shi, Pengcheng

    2013-01-01

    Embryonic heart morphogenesis (EHM) is a complex and dynamic process where the heart transforms from a single tube into a four-chambered pump. This process is of great biological and clinical interest but is still poorly understood for two main reasons. On the one hand, the existing imaging modalities for investigating EHM suffered from either limited penetration depth or limited spatial resolution. On the other hand, current works typically adopted manual segmentation, which was tedious, subjective, and time consuming considering the complexity of developing heart geometry and the large size of images. In this paper, we propose to utilize confocal microscopy imaging with tissue optical immersion clearing technique to image the heart at different stages of development for EHM study. The imaging method is able to produce high spatial resolution images and achieve large penetration depth at the same time. Furthermore, we propose a novel convex active contour model for automatic image segmentation. The model has the ability to deal with intensity fall-off in depth which is characterized by confocal microscopy images. We acquired the images of embryonic quail hearts from day 6 to day 14 of incubation for EHM study. The experimental results were promising and provided us with an insight view of early heart growth pattern and also paved the road for data-driven heart growth modeling. PMID:24454530

  10. 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.

  11. Quantification of embryonic atrioventricular valve biomechanics during morphogenesis.

    PubMed

    Buskohl, Philip R; Gould, Russell A; Butcher, Jonathan T

    2012-03-15

    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

  12. Mammalian Pumilio 2 regulates dendrite morphogenesis and synaptic function

    PubMed Central

    Schoderboeck, Lucia; Gingl, Ewald; Luzi, Ettore; Riefler, Julia; Di Leva, Francesca; Karra, Daniela; Thomas, Sabine; Kiebler, Michael A.; Macchi, Paolo

    2010-01-01

    In Drosophila, Pumilio (Pum) is important for neuronal homeostasis as well as learning and memory. We have recently characterized a mammalian homolog of Pum, Pum2, which is found in discrete RNA-containing particles in the somatodendritic compartment of polarized neurons. In this study, we investigated the role of Pum2 in developing and mature neurons by RNA interference. In immature neurons, loss of Pum2 led to enhanced dendritic outgrowth and arborization. In mature neurons, Pum2 down-regulation resulted in a significant reduction in dendritic spines and an increase in elongated dendritic filopodia. Furthermore, we observed an increase in excitatory synapse markers along dendritic shafts. Electrophysiological analysis of synaptic function of neurons lacking Pum2 revealed an increased miniature excitatory postsynaptic current frequency. We then identified two specific mRNAs coding for a known translational regulator, eIF4E, and for a voltage-gated sodium channel, Scn1a, which interacts with Pum2 in immunoprecipitations from brain lysates. Finally, we show that Pum2 regulates translation of the eIF4E mRNA. Taken together, our data reveal a previously undescribed role for Pum2 in dendrite morphogenesis, synapse function, and translational control. PMID:20133610

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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. PMID:25745427

  18. 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).

  19. Twist1 Is Essential for Tooth Morphogenesis and Odontoblast Differentiation.

    PubMed

    Meng, Tian; Huang, Yanyu; Wang, Suzhen; Zhang, Hua; Dechow, Paul C; Wang, Xiaofang; Qin, Chunlin; Shi, Bing; D'Souza, Rena N; Lu, Yongbo

    2015-12-01

    Twist1 is a basic helix-loop-helix-containing transcription factor that is expressed in the dental mesenchyme during the early stages of tooth development. To better delineate its roles in tooth development, we generated Twist1 conditional knockout embryos (Twist2(Cre) (/+);Twist1(fl/fl)) by breeding Twist1 floxed mice (Twist1(fl/fl)) with Twist2-Cre recombinase knockin mice (Twist2(Cre) (/+)). The Twist2(Cre) (/+);Twist1(fl/fl) embryos formed smaller tooth germs and abnormal cusps during early tooth morphogenesis. Molecular and histological analyses showed that the developing molars of the Twist2(Cre) (/+);Twist1(fl/fl) embryos had reduced cell proliferation and expression of fibroblast growth factors 3, 4, 9, and 10 and FGF receptors 1 and 2 in the dental epithelium and mesenchyme. In addition, 3-week-old renal capsular transplants of embryonic day 18.5 Twist2(Cre) (/+);Twist1(fl/fl) molars showed malformed crowns and cusps with defective crown dentin and enamel. Immunohistochemical analyses revealed that the implanted mutant molars had defects in odontoblast differentiation and delayed ameloblast differentiation. Furthermore, in vitro ChIP assays demonstrated that Twist1 was able to bind to a specific region of the Fgf10 promoter. In conclusion, our findings suggest that Twist1 plays crucial roles in regulating tooth development and that it may exert its functions through the FGF signaling pathway. PMID:26487719

  20. Translational Control of Mitochondrial Energy Production Mediates Neuron Morphogenesis

    PubMed Central

    Oruganty-Das, Aparna; Ng, Teclise; Udagawa, Tsuyoshi; Goh, Eyleen L.K.; Richter, Joel D.

    2012-01-01

    SUMMARY Mitochondrial energy production is a tightly regulated process involving the coordinated transcription of several genes, catalysis of a plethora of posttranslational modifications, and the formation of very large molecular supercomplexes. The regulation of mitochondrial activity is particularly important for the brain, which is a high-energy-consuming organ that depends on oxidative phosphorylation to generate ATP. Here we show that brain mitochondrial ATP production is controlled by the cytoplasmic polyadenylation-induced translation of an mRNA encoding NDUFV2, a key mitochondrial protein. Knockout mice lacking the Cytoplasmic Polyadenylation Element Binding protein 1 (CPEB1) have brain-specific dysfunctional mitochondria and reduced ATP levels, which is due to defective polyadenylation-induced translation of electron transport chain complex I protein NDUFV2 mRNA. This reduced ATP results in defective dendrite morphogenesis of hippocampal neurons both in vitro and in vivo. These and other results demonstrate that CPEB1 control of mitochondrial activity is essential for normal brain development. PMID:23217258

  1. Compensatory branching morphogenesis of stalk cells in the Drosophila trachea

    PubMed Central

    Francis, Deanne; Ghabrial, Amin S.

    2015-01-01

    ABSTRACT Tubes are essential for nutrient transport and gas exchange in multicellular eukaryotes, but how connections between different tube types are maintained over time is unknown. In the Drosophila tracheal system, mutations in oak gall (okg) and conjoined (cnj) confer identical defects, including late onset blockage near the terminal cell-stalk cell junction and the ectopic extension of autocellular, seamed tubes into the terminal cell. We determined that okg and cnj encode the E and G subunits of the vacuolar ATPase (vATPase) and showed that both the V0 and V1 domains are required for terminal cell morphogenesis. Remarkably, the ectopic seamed tubes running along vATPase-deficient terminal cells belonged to the neighboring stalk cells. All vATPase-deficient tracheal cells had reduced apical domains and terminal cells displayed mislocalized apical proteins. Consistent with recent reports that the mTOR and vATPase pathways intersect, we found that mTOR pathway mutants phenocopied okg and cnj. Furthermore, terminal cells depleted for the apical determinants Par6 or aPKC had identical ectopic seamed tube defects. We thus identify a novel mechanism of compensatory branching in which stalk cells extend autocellular tubes into neighboring terminal cells with undersized apical domains. This compensatory branching also occurs in response to injury, with damaged terminal cells being rapidly invaded by their stalk cell neighbor. PMID:25977367

  2. 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

  3. 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

  4. 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

  5. Diversity of epithelial morphogenesis during eggshell formation in drosophilids

    PubMed Central

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

    2015-01-01

    ABSTRACT The eggshells of drosophilid species provide a powerful model for studying the origins of morphological diversity. The dorsal appendages, or respiratory filaments, of these eggshells display a remarkable interspecies variation in number and shape, and the epithelial patterning underlying the formation of these structures is an area of active research. To extend the analysis of dorsal appendage formation to include morphogenesis, we developed an improved 3D image reconstruction approach. This approach revealed considerable interspecies variation in the cell shape changes and neighbor exchanges underlying appendage formation. Specifically, although the appendage floor in Drosophila melanogaster is formed through spatially ordered neighbor exchanges, the same structure in Scaptodrosophila pattersoni is formed through extreme changes in cell shape, whereas Drosophila funebris appears to display a combination of both cellular mechanisms. Furthermore, localization patterns of Par3/Bazooka suggest a self-organized, cell polarity-based origin for the variability of appendage number in S. pattersoni. Our results suggest that species deploy different combinations of apically and basally driven mechanisms to convert a two-dimensional primordium into a three-dimensional structure, and provide new directions for exploring the molecular origins of interspecies morphological variation. PMID:25953345

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

    PubMed Central

    Dong, Xintong; Liu, Oliver W.; Howell, Audrey S.; Shen, Kang

    2014-01-01

    Summary 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 C. 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, while 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

  7. 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

  8. 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

  9. 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

  10. Compensatory branching morphogenesis of stalk cells in the Drosophila trachea.

    PubMed

    Francis, Deanne; Ghabrial, Amin S

    2015-06-01

    Tubes are essential for nutrient transport and gas exchange in multicellular eukaryotes, but how connections between different tube types are maintained over time is unknown. In the Drosophila tracheal system, mutations in oak gall (okg) and conjoined (cnj) confer identical defects, including late onset blockage near the terminal cell-stalk cell junction and the ectopic extension of autocellular, seamed tubes into the terminal cell. We determined that okg and cnj encode the E and G subunits of the vacuolar ATPase (vATPase) and showed that both the V0 and V1 domains are required for terminal cell morphogenesis. Remarkably, the ectopic seamed tubes running along vATPase-deficient terminal cells belonged to the neighboring stalk cells. All vATPase-deficient tracheal cells had reduced apical domains and terminal cells displayed mislocalized apical proteins. Consistent with recent reports that the mTOR and vATPase pathways intersect, we found that mTOR pathway mutants phenocopied okg and cnj. Furthermore, terminal cells depleted for the apical determinants Par6 or aPKC had identical ectopic seamed tube defects. We thus identify a novel mechanism of compensatory branching in which stalk cells extend autocellular tubes into neighboring terminal cells with undersized apical domains. This compensatory branching also occurs in response to injury, with damaged terminal cells being rapidly invaded by their stalk cell neighbor. PMID:25977367

  11. 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

  12. 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.

  13. Cellular analysis of cleavage-stage chick embryos reveals hidden conservation in vertebrate early development.

    PubMed

    Nagai, Hiroki; Sezaki, Maiko; Kakiguchi, Kisa; Nakaya, Yukiko; Lee, Hyung Chul; Ladher, Raj; Sasanami, Tomohiro; Han, Jae Yong; Yonemura, Shigenobu; Sheng, Guojun

    2015-04-01

    Birds and mammals, phylogenetically close amniotes with similar post-gastrula development, exhibit little conservation in their post-fertilization cleavage patterns. Data from the mouse suggest that cellular morphogenesis and molecular signaling at the cleavage stage play important roles in lineage specification at later (blastula and gastrula) stages. Very little is known, however, about cleavage-stage chick embryos, owing to their poor accessibility. This period of chick development takes place before egg-laying and encompasses several fundamental processes of avian embryology, including zygotic gene activation (ZGA) and blastoderm cell-layer increase. We have carried out morphological and cellular analyses of cleavage-stage chick embryos covering the first half of pre-ovipositional development, from Eyal-Giladi and Kochav stage (EGK-) I to EGK-V. Scanning electron microscopy revealed remarkable subcellular details of blastomere cellularization and subgerminal cavity formation. Phosphorylated RNA polymerase II immunostaining showed that ZGA in the chick starts at early EGK-III during the 7th to 8th nuclear division cycle, comparable with the time reported for other yolk-rich vertebrates (e.g. zebrafish and Xenopus). The increase in the number of cell layers after EGK-III is not a direct consequence of oriented cell division. Finally, we present evidence that, as in the zebrafish embryo, a yolk syncytial layer is formed in the avian embryo after EGK-V. Our data suggest that several fundamental features of cleavage-stage development in birds resemble those in yolk-rich anamniote species, revealing conservation in vertebrate early development. Whether this conservation lends morphogenetic support to the anamniote-to-amniote transition in evolution or reflects developmental plasticity in convergent evolution awaits further investigation. PMID:25742796

  14. Cellular analysis of cleavage-stage chick embryos reveals hidden conservation in vertebrate early development

    PubMed Central

    Nagai, Hiroki; Sezaki, Maiko; Kakiguchi, Kisa; Nakaya, Yukiko; Lee, Hyung Chul; Ladher, Raj; Sasanami, Tomohiro; Han, Jae Yong; Yonemura, Shigenobu; Sheng, Guojun

    2015-01-01

    Birds and mammals, phylogenetically close amniotes with similar post-gastrula development, exhibit little conservation in their post-fertilization cleavage patterns. Data from the mouse suggest that cellular morphogenesis and molecular signaling at the cleavage stage play important roles in lineage specification at later (blastula and gastrula) stages. Very little is known, however, about cleavage-stage chick embryos, owing to their poor accessibility. This period of chick development takes place before egg-laying and encompasses several fundamental processes of avian embryology, including zygotic gene activation (ZGA) and blastoderm cell-layer increase. We have carried out morphological and cellular analyses of cleavage-stage chick embryos covering the first half of pre-ovipositional development, from Eyal-Giladi and Kochav stage (EGK-) I to EGK-V. Scanning electron microscopy revealed remarkable subcellular details of blastomere cellularization and subgerminal cavity formation. Phosphorylated RNA polymerase II immunostaining showed that ZGA in the chick starts at early EGK-III during the 7th to 8th nuclear division cycle, comparable with the time reported for other yolk-rich vertebrates (e.g. zebrafish and Xenopus). The increase in the number of cell layers after EGK-III is not a direct consequence of oriented cell division. Finally, we present evidence that, as in the zebrafish embryo, a yolk syncytial layer is formed in the avian embryo after EGK-V. Our data suggest that several fundamental features of cleavage-stage development in birds resemble those in yolk-rich anamniote species, revealing conservation in vertebrate early development. Whether this conservation lends morphogenetic support to the anamniote-to-amniote transition in evolution or reflects developmental plasticity in convergent evolution awaits further investigation. PMID:25742796

  15. Seven years' experience with etidronate in a woman with anorexia nervosa and vertebral fractures.

    PubMed

    Iwamoto, Jun; Sato, Yoshihiro; Uzawa, Mitsuyoshi; Takeda, Tsuyoshi; Matsumoto, Hideo

    2011-01-01

    We report the case of a 30-year-old Japanese woman with anorexia nervosa and vertebral fractures who was treated with etidronate. She had a history of anorexia nervosa, chronic back pain, osteoporosis, and multiple vertebral fractures (morphometric fractures) that responded poorly to treatment with alfacalcidol (1 μg daily) for 1 year and was treated with cyclical etidronate (200 mg for 2 weeks every 3 months) for 7 years. The lumbar spine bone mineral density (BMD) increased, and the serum alkaline phosphatase and urinary cross-linked N-terminal telopeptides of type I collagen levels and back pain decreased. During the 7-year period of treatment with etidronate, no osteoporotic fractures occurred. The patient experienced neither renal dysfunction nor hyperparathyroidism caused by osteomalacia. No gastrointestinal tract symptoms were observed. Thus, etidronate was effective for increasing the lumbar spine BMD and reducing back pain over a 7-year period without causing either osteoporotic fractures or adverse events. PMID:21845050

  16. Seven years’ experience with etidronate in a woman with anorexia nervosa and vertebral fractures

    PubMed Central

    Iwamoto, Jun; Sato, Yoshihiro; Uzawa, Mitsuyoshi; Takeda, Tsuyoshi; Matsumoto, Hideo

    2011-01-01

    We report the case of a 30-year-old Japanese woman with anorexia nervosa and vertebral fractures who was treated with etidronate. She had a history of anorexia nervosa, chronic back pain, osteoporosis, and multiple vertebral fractures (morphometric fractures) that responded poorly to treatment with alfacalcidol (1 μg daily) for 1 year and was treated with cyclical etidronate (200 mg for 2 weeks every 3 months) for 7 years. The lumbar spine bone mineral density (BMD) increased, and the serum alkaline phosphatase and urinary cross-linked N-terminal telopeptides of type I collagen levels and back pain decreased. During the 7-year period of treatment with etidronate, no osteoporotic fractures occurred. The patient experienced neither renal dysfunction nor hyperparathyroidism caused by osteomalacia. No gastrointestinal tract symptoms were observed. Thus, etidronate was effective for increasing the lumbar spine BMD and reducing back pain over a 7-year period without causing either osteoporotic fractures or adverse events. PMID:21845050

  17. Coelomic epithelium-derived cells in visceral morphogenesis.

    PubMed

    Ariza, Laura; Carmona, Rita; Cañete, Ana; Cano, Elena; Muñoz-Chápuli, Ramón

    2016-03-01

    Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans. PMID:26638186

  18. 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

  19. 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

  20. 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

  1. Intra-arterial Onyx Embolization of Vertebral Body Lesions

    PubMed Central

    Sedora-Roman, Neda I.; Reddy, Arra Suresh; Ogilvy, Christopher S.; Thomas, Ajith J.

    2013-01-01

    While Onyx embolization of cerebrospinal arteriovenous shunts is well-established, clinical researchers continue to broaden applications to other vascular lesions of the neuraxis. This report illustrates the application of Onyx (eV3, Plymouth, MN) embolization to vertebral body lesions, specifically, a vertebral hemangioma and renal cell carcinoma vertebral body metastatic lesion. PMID:24729960

  2. Higher prevalence of morphometric vertebral fractures in patients with recent coronary events independently of BMD measurements.

    PubMed

    Silva, Henrique C; Pinheiro, Marcelo M; Genaro, Patrícia S; Castro, Charlles H M; Monteiro, Carlos M C; Fonseca, Francisco A H; Szejnfeld, Vera L

    2013-02-01

    Cardiovascular disease and osteoporosis are important causes of morbi-mortality in the elderly and may be mutually related. Low bone mineral density (BMD) may be associated with increased risk of cardiovascular events. We investigated the prevalence of low bone mass and fractures in metabolic syndrome patients with acute coronary events. A case-control study was conducted with 150 individuals (30-80years-old) with metabolic syndrome. Seventy-one patients had had an acute coronary syndrome episode in the last 6months (cases) and the remaining 79 had no coronary event (controls). Cases and controls were matched for gender, BMI and age. DXA measurements and body composition were performed while spine radiographs surveyed for vertebral fractures and vascular calcification. Biochemical bone and metabolic parameters were measured in all patients. No statistically significant difference in BMD and the prevalence of osteopenia, osteoporosis and non-vertebral fractures was observed between cases and controls. The prevalence of vertebral fractures and all fractures was higher in the cases (14.1 versus 1.3%, p=0.003 and 22.5versus7.6%, p=0.010, respectively). Male gender (OR=0.22 95% CI 0.58 to 0.83, p=0.026) and daily intake of more than 3 portions of dairy products (OR=0.19 95% CI 0.49 to 0.75, p=0.017) were associated with lower prevalence of fractures. Cases had higher risk for fractures (OR=4.97, 95% CI 1.17 to 30.30, p=0.031). Bone mass and body composition parameters were not associated with cardiovascular risk factors or bone mineral metabolism. Patients with fragility fractures had higher OPG serum levels than those without fractures (p<0.001). Our findings demonstrated that patients with recent coronary events have a higher prevalence of vertebral fractures independently of BMD. PMID:23142805

  3. 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

  4. 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

  5. Thyroid Dysfunction in an Adult Female Population: A population-based study of Latin American Vertebral Osteoporosis Study (LAVOS) - Puerto Rico Site Hypothyroidism in LAVOS-Puerto Rico site

    PubMed Central

    González-Rodríguez, Loida A.; Felici-Giovanini, Marcos E; Haddock, Lillian

    2013-01-01

    Objective To determine the prevalence of hypothyroidism in an adult female population in Puerto Rico and to determine the relationship between hypothyroidism, bone mineral density and vertebral and non-vertebral fractures in this population. Methods Data from the 400 subjects database of the Latin American Vertebral Osteoporosis Study (LAVOS), Puerto Rico site was reviewed. Patient’s medical history, anthropometric data, current medications, laboratories, and DXA results was extracted. Subjects with thyroid dysfunction were identified based on their previous medical history and levels of TSH. Bone Mineral Density was classified using the World Health Organization criteria. Crude prevalence of thyroid dysfunction were estimated with a confidence of 95% and weighted by the population distribution by age, according to the distribution by age group in the 2000 census. Bone mineral densities and prevalence of vertebral and non-vertebral fractures were compared among the groups. Results The weighted prevalence of hyperthyroidism in this population was 0.0043% (95% CI: −0.0021%, 0.0107%). The weighted prevalence of hypothyroidism was 24.2% (95% CI: 19.9%, 28.4%). Increased prevalence of hypothyroidism was found in participants 70 years or older. The mean BMD at spine, hip and femoral neck was similar among the groups. No difference in the proportion of participants with vertebral and non-vertebral fractures was found among the groups. Conclusion Our study found a high prevalence of hypothyroidism among adult postmenopausal females in Puerto Rico. No association between hypothyroidism and decreased bone mineral densities, vertebral or non-vertebral fractures was found in this population. PMID:23781620

  6. Embryonic vascular development: immunohistochemical identification of the origin and subsequent morphogenesis of the major vessel primordia in quail embryos.

    PubMed

    Coffin, J D; Poole, T J

    1988-04-01

    The development of the embryonic vasculature is examined here using a monoclonal antibody, QH-1, capable of labelling the presumptive endothelial cells of Japanese quail embryos. Antibody labelling is first seen within the embryo proper at the 1-somite stage. Scattered labelling of single cells appears ventral to the somites and at the lateral edges of the anterior intestinal portal. The dorsal aorta soon forms a continuous cord at the ventrolateral edge of the somites and continues into the head to fuse with the ventral aorta forming the first aortic arch by the 6-somite stage. The rudiments of the endocardium fuse at the midline above the anterior intestinal portal by the 3-somite stage and the ventral aorta extends craniad. Intersomitic arteries begin to sprout off of the dorsal aorta at the 7-somite stage. The posterior cardinal vein forms from single cells which segregate from somatic mesoderm at the 7-somite stage to form a loose plexus which moves mediad and wraps around the developing Wolffian duct in later stages. These studies suggest two modes of origin of embryonic blood vessels. The dorsal aortae and cardinal veins apparently arise in situ by the local segregation of presumptive endothelial cells from the mesoderm. The intersomitic arteries, vertebral arteries and cephalic vasculature arise by sprouts from these early vessel rudiments. There also seems to be some cell migration in the morphogenesis of endocardium, ventral aorta and aortic arches. The extent of presumptive endothelial migration in these cases, however, needs to be clarified by microsurgical intervention. PMID:3048971

  7. New Minerals and Science.

    ERIC Educational Resources Information Center

    Birch, William D.

    1997-01-01

    Defines geodiversity, compares it to biodiversity, and discusses the mineral classification system. Charts the discovery of new minerals in Australia over time and focuses on uses of these minerals in technological advances. (DDR)

  8. Mineral spirits poisoning

    MedlinePlus

    Mineral spirits are liquid chemicals used to thin paint and as a degreaser. Mineral spirits poisoning occurs ... be found in: Mineral spirits ( Stoddard solvent ) Some paints Some floor and furniture waxes and polishes Some ...

  9. Rocks and Minerals.

    ERIC Educational Resources Information Center

    Naturescope, 1987

    1987-01-01

    Provides background information on rocks and minerals, including the unique characteristics of each. Teaching activities on rock-hunting and identification, mineral configurations, mystery minerals, and growing crystals are provided. Reproducible worksheets are included for two of the activities. (TW)

  10. Dynamic Evolution of the LPS-Detoxifying Enzyme Intestinal Alkaline Phosphatase in Zebrafish and Other Vertebrates

    PubMed Central

    Yang, Ye; Wandler, Anica M.; Postlethwait, John H.; Guillemin, Karen

    2012-01-01

    Alkaline phosphatases (Alps) are well-studied enzymes that remove phosphates from a variety of substrates. Alps function in diverse biological processes, including modulating host-bacterial interactions by dephosphorylating the Gram-negative bacterial cell wall component lipopolysaccharide (LPS). In animals, Alps are encoded by multiple genes characterized by either ubiquitous expression (named Alpls for their liver expression, but a key to proper bone mineralization), or their tissue-specific expression, for example in the intestine (Alpi). We previously characterized a zebrafish alpi gene (renamed here alpi.1) that is regulated by Myd88-dependent innate immune signaling and that is required to prevent a host’s excessive inflammatory reactions to its resident microbiota. Here we report the characterization of two new alp genes in zebrafish, alpi.2 and alp3. To understand their origins, we investigated the phylogenetic history of Alp genes in animals. We find that vertebrate Alp genes are organized in three clades with one of these clades missing from the mammals. We present evidence that these three clades originated during the two vertebrate genome duplications. We show that alpl is ubiquitously expressed in zebrafish, as it is in mammals, whereas the other three alps are specific to the intestine. Our phylogenetic analysis reveals that in contrast to Alpl, which has been stably maintained as a single gene throughout the vertebrates, the Alpis have been lost and duplicated multiple times independently in vertebrate lineages, likely reflecting the rapid and dynamic evolution of vertebrate gut morphologies, driven by changes in bacterial associations and diet. PMID:23091474

  11. ECM signaling regulates collective cellular dynamics to control pancreas branching morphogenesis

    PubMed Central

    Shih, Hung Ping; Panlasigui, Devin; Cirulli, Vincenzo; Sander, Maike

    2015-01-01

    Summary During pancreas development, epithelial buds undergo branching morphogenesis to form an exocrine and endocrine gland. Proper morphogenesis is necessary for correct lineage allocation of pancreatic progenitors; however, the cellular events underlying pancreas morphogenesis are unknown. Here, we employed time-lapse microscopy and fluorescent labeling of cells to analyze cell behaviors associated with pancreas morphogenesis. We observed that outer bud cells adjacent to the basement membrane are pleomorphic and rearrange frequently; as well, they largely remain in the outer cell compartment even after mitosis. These cell behaviors and pancreas branching depend on cell contacts with the basement membrane, which induce actomyosin cytoskeleton remodeling via integrin-mediated activation of FAK/Src signaling. We show that integrin signaling reduces E-cadherin-mediated cell-cell adhesion in outer cells, and provide genetic evidence that this regulation is necessary for initiation of branching. Our study suggests that regulation of cell motility and adhesion by local niche cues initiates pancreas branching morphogenesis. PMID:26748698

  12. Species-specific contribution of volumetric growth and tissue convergence to posterior body elongation in vertebrates.

    PubMed

    Steventon, Ben; Duarte, Fernando; Lagadec, Ronan; Mazan, Sylvie; Nicolas, Jean-François; Hirsinger, Estelle

    2016-05-15

    Posterior body elongation is a widespread mechanism propelling the generation of the metazoan body plan. The posterior growth model predicts that a posterior growth zone generates sufficient tissue volume to elongate the posterior body. However, there are energy supply-related differences between vertebrates in the degree to which growth occurs concomitantly with embryogenesis. By applying a multi-scalar morphometric analysis in zebrafish embryos, we show that posterior body elongation is generated by an influx of cells from lateral regions, by convergence-extension of cells as they exit the tailbud, and finally by a late volumetric growth in the spinal cord and notochord. Importantly, the unsegmented region does not generate additional tissue volume. Fibroblast growth factor inhibition blocks tissue convergence rather than volumetric growth, showing that a conserved molecular mechanism can control convergent morphogenesis through different cell behaviours. Finally, via a comparative morphometric analysis in lamprey, dogfish, zebrafish and mouse, we propose that elongation via posterior volumetric growth is linked to increased energy supply and is associated with an overall increase in volumetric growth and elongation. PMID:26989170

  13. 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

  14. 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

  15. Floral morphogenesis: stochastic explorations of a gene network epigenetic landscape.

    PubMed

    Alvarez-Buylla, Elena R; Chaos, Alvaro; Aldana, Maximino; Benítez, Mariana; Cortes-Poza, Yuriria; Espinosa-Soto, Carlos; Hartasánchez, Diego A; Lotto, R Beau; Malkin, David; Escalera Santos, Gerardo J; Padilla-Longoria, Pablo

    2008-01-01

    In contrast to the classical view of development as a preprogrammed and deterministic process, recent studies have demonstrated that stochastic perturbations of highly non-linear systems may underlie the emergence and stability of biological patterns. Herein, we address the question of whether noise contributes to the generation of the stereotypical temporal pattern in gene expression during flower development. We modeled the regulatory network of organ identity genes in the Arabidopsis thaliana flower as a stochastic system. This network has previously been shown to converge to ten fixed-point attractors, each with gene expression arrays that characterize inflorescence cells and primordial cells of sepals, petals, stamens, and carpels. The network used is binary, and the logical rules that govern its dynamics are grounded in experimental evidence. We introduced different levels of uncertainty in the updating rules of the network. Interestingly, for a level of noise of around 0.5-10%, the system exhibited a sequence of transitions among attractors that mimics the sequence of gene activation configurations observed in real flowers. We also implemented the gene regulatory network as a continuous system using the Glass model of differential equations, that can be considered as a first approximation of kinetic-reaction equations, but which are not necessarily equivalent to the Boolean model. Interestingly, the Glass dynamics recover a temporal sequence of attractors, that is qualitatively similar, although not identical, to that obtained using the Boolean model. Thus, time ordering in the emergence of cell-fate patterns is not an artifact of synchronous updating in the Boolean model. Therefore, our model provides a novel explanation for the emergence and robustness of the ubiquitous temporal pattern of floral organ specification. It also constitutes a new approach to understanding morphogenesis, providing predictions on the population dynamics of cells with different

  16. Multiscale Feature Analysis of Salivary Gland Branching Morphogenesis

    PubMed Central

    Baydil, Banu; Daley, William P.; Larsen, Melinda; Yener, Bülent

    2012-01-01

    Pattern formation in developing tissues involves dynamic spatio-temporal changes in cellular organization and subsequent evolution of functional adult structures. Branching morphogenesis is a developmental mechanism by which patterns are generated in many developing organs, which is controlled by underlying molecular pathways. Understanding the relationship between molecular signaling, cellular behavior and resulting morphological change requires quantification and categorization of the cellular behavior. In this study, tissue-level and cellular changes in developing salivary gland in response to disruption of ROCK-mediated signaling by are modeled by building cell-graphs to compute mathematical features capturing structural properties at multiple scales. These features were used to generate multiscale cell-graph signatures of untreated and ROCK signaling disrupted salivary gland organ explants. From confocal images of mouse submandibular salivary gland organ explants in which epithelial and mesenchymal nuclei were marked, a multiscale feature set capturing global structural properties, local structural properties, spectral, and morphological properties of the tissues was derived. Six feature selection algorithms and multiway modeling of the data was performed to identify distinct subsets of cell graph features that can uniquely classify and differentiate between different cell populations. Multiscale cell-graph analysis was most effective in classification of the tissue state. Cellular and tissue organization, as defined by a multiscale subset of cell-graph features, are both quantitatively distinct in epithelial and mesenchymal cell types both in the presence and absence of ROCK inhibitors. Whereas tensor analysis demonstrate that epithelial tissue was affected the most by inhibition of ROCK signaling, significant multiscale changes in mesenchymal tissue organization were identified with this analysis that were not identified in previous biological studies. We

  17. A Computational Approach to Understand In Vitro Alveolar Morphogenesis

    PubMed Central

    Kim, Sean H. J.; Yu, Wei; Mostov, Keith; Matthay, Michael A.; Hunt, C. Anthony

    2009-01-01

    Primary human alveolar type II (AT II) epithelial cells maintained in Matrigel cultures form alveolar-like cysts (ALCs) using a cytogenesis mechanism that is different from that of other studied epithelial cell types: neither proliferation nor death is involved. During ALC formation, AT II cells engage simultaneously in fundamentally different, but not fully characterized activities. Mechanisms enabling these activities and the roles they play during different process stages are virtually unknown. Identifying, characterizing, and understanding the activities and mechanisms are essential to achieving deeper insight into this fundamental feature of morphogenesis. That deeper insight is needed to answer important questions. When and how does an AT cell choose to switch from one activity to another? Why does it choose one action rather than another? We report obtaining plausible answers using a rigorous, multi-attribute modeling and simulation approach that leveraged earlier efforts by using new, agent and object-oriented capabilities. We discovered a set of cell-level operating principles that enabled in silico cells to self-organize and generate systemic cystogenesis phenomena that are quantitatively indistinguishable from those observed in vitro. Success required that the cell components be quasi-autonomous. As simulation time advances, each in silico cell autonomously updates its environment information to reclassify its condition. It then uses the axiomatic operating principles to execute just one action for each possible condition. The quasi-autonomous actions of individual in silico cells were sufficient for developing stable cyst-like structures. The results strengthen in silico to in vitro mappings at three levels: mechanisms, behaviors, and operating principles, thereby achieving a degree of validation and enabling answering the questions posed. We suggest that the in silico operating principles presented may have a biological counterpart and that a

  18. 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

  19. Involvement of ESCRT-II in Hepatitis B Virus Morphogenesis

    PubMed Central

    Stieler, Jens T.; Prange, Reinhild

    2014-01-01

    The hepatitis B virus (HBV) is an enveloped DNA virus that replicates via reverse transcription of its pregenomic RNA (pgRNA). Budding of HBV is supposed to occur at intracellular membranes and requires scission functions of the endosomal sorting complex required for transport (ESCRT) provided by ESCRT-III and VPS4. Here, we have investigated the impact of the upstream-acting ESCRT-I and ESCRT-II complexes in HBV morphogenesis. RNA interference knockdown of the ESCRT-I subunits TSG101 and VPS28 did not block, but rather stimulate virus release. In contrast, RNAi-mediated depletion of the ESCRT-II components EAP20, EAP30 and EAP45 greatly reduced virus egress. By analyzing different steps of the HBV maturation pathway, we find that the knockdown of ESCRT-II not only inhibited the production and/or release of enveloped virions, but also impaired intracellular nucleocapsid formation. Transcription/translation studies revealed that the depletion of ESCRT-II neither affected the synthesis and nuclear export of HBV-specific RNAs nor the expression of the viral core and envelope proteins. Moreover, the absence of ESCRT-II had no effects on the assembly capability and integrity of HBV core/capsids. However, the level of encapsidated pgRNA was significantly reduced in ESCRT-II-depleted cells, implicating that ESCRT-II directs steps accompanying the formation of replication-competent nucleocapsids, like e.g. assisting in RNA trafficking and encapsidation. In support of this, the capsid protein was found to interact and colocalize with ESCRT-II subunits in virus-producing cells. Together, these results indicate an essential role for ESCRT-II in the HBV life cycle and suggest that ESCRT-II functions prior to the final HBV budding reaction. PMID:24614091

  20. 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

  1. 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.

  2. Cholesterol-binding viral proteins in virus entry and morphogenesis.

    PubMed

    Schroeder, Cornelia

    2010-01-01

    Up to now less than a handful of viral cholesterol-binding proteins have been characterized, in HIV, influenza virus and Semliki Forest virus. These are proteins with roles in virus entry or morphogenesis. In the case of the HIV fusion protein gp41 cholesterol binding is attributed to a cholesterol recognition consensus (CRAC) motif in a flexible domain of the ectodomain preceding the trans-membrane segment. This specific CRAC sequence mediates gp41 binding to a cholesterol affinity column. Mutations in this motif arrest virus fusion at the hemifusion stage and modify the ability of the isolated CRAC peptide to induce segregation of cholesterol in artificial membranes.Influenza A virus M2 protein co-purifies with cholesterol. Its proton translocation activity, responsible for virus uncoating, is not cholesterol-dependent, and the transmembrane channel appears too short for integral raft insertion. Cholesterol binding may be mediated by CRAC motifs in the flexible post-TM domain, which harbours three determinants of binding to membrane rafts. Mutation of the CRAC motif of the WSN strain attenuates virulence for mice. Its affinity to the raft-non-raft interface is predicted to target M2 protein to the periphery of lipid raft microdomains, the sites of virus assembly. Its influence on the morphology of budding virus implicates M2 as factor in virus fission at the raft boundary. Moreover, M2 is an essential factor in sorting the segmented genome into virus particles, indicating that M2 also has a role in priming the outgrowth of virus buds.SFV E1 protein is the first viral type-II fusion protein demonstrated to directly bind cholesterol when the fusion peptide loop locks into the target membrane. Cholesterol binding is modulated by another, proximal loop, which is also important during virus budding and as a host range determinant, as shown by mutational studies. PMID:20213541

  3. 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.

  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. 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.

  6. [A vertebral arteriovenous fistula diagnosed by auscultation].

    PubMed

    Iglesias Escalera, G; Diaz-Delgado Peñas, R; Carrasco Marina, M Ll; Maraña Perez, A; Ialeggio, D

    2015-01-01

    Cervical artery fistulas are rare arteriovenous malformations. The etiology of the vertebral arteriovenous fistulas (AVF) can be traumatic or spontaneous. They tend to be asymptomatic or palpation or continuous vibration in the cervical region. An arteriography is necessary for a definitive diagnosis. The treatment is complete embolization of the fistula. We present the case of a two year-old male, where the mother described it «like a washing machine in his head». On palpation during the physical examination, there was a continuous vibration, and a continuous murmur in left cervical region. A vascular malformation in vertebral region was clinically suspected, and confirmed with angio-MRI and arteriography. AVF are rare in childhood. They should be suspected in the presence of noises, palpation or continuous vibration in the cervical region. Early diagnosis can prevent severe complications in asymptomatic children. PMID:24598790

  7. Vertebral osteomyelitis: disk hypodensity on CT

    SciTech Connect

    Larde, D.; Mathieu, D.; Frija, J.; Gaston, A.; Vasile, N.

    1982-11-01

    The importance and role of computed tomography (CT) are discussed on the basis of 36 cases of vertebral osteomyelitis. The bone images themselves, the detection of lumbar disk hypodensity, and the exploration of soft paraspinal regions in the search for an abscess are factors that contribute to the superiority of this method in difficult cases. In cases where the diagnosis is already known, CT offers an excellent method to assess the extent of the lesions. Its accuracy, coupled with its rapidity and noninvasive nature, affects the role of conventional tomography, a method that is incomplete and involves higher radiation doses. CT offers an excellent method for follow-up after treatment of vertebral osteomyelitis.

  8. 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

  9. Acute compressive myelopathy due to vertebral haemangioma

    PubMed Central

    Macki, Mohamed; Bydon, Mohamad; Kaloostian, Paul; Bydon, Ali

    2014-01-01

    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. PMID:24777075

  10. On the pathway of mineral deposition in larval zebrafish caudal fin bone.

    PubMed

    Akiva, Anat; Malkinson, Guy; Masic, Admir; Kerschnitzki, Michael; Bennet, Mathieu; Fratzl, Peter; Addadi, Lia; Weiner, Steve; Yaniv, Karina

    2015-06-01

    A poorly understood aspect of bone biomineralization concerns the mechanisms whereby ions are sequestered from the environment, concentrated, and deposited in the extracellular matrix. In this study, we follow mineral deposition in the caudal fin of the zebrafish larva in vivo. Using fluorescence and cryo-SEM-microscopy, in combination with Raman and XRF spectroscopy, we detect the presence of intracellular mineral particles located between bones, and in close association with blood vessels. Calcium-rich particles are also located away from the mineralized bone, and these are also in close association with blood vessels. These observations challenge the view that mineral formation is restricted to osteoblast cells juxtaposed to bone, or to the extracellular matrix. Our results, derived from observations performed in living animals, contribute a new perspective to the comprehensive mechanism of bone formation in vertebrates, from the blood to the bone. More broadly, these findings may shed light on bone mineralization processes in other vertebrates, including humans. PMID:25725266

  11. 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

  12. 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

  13. Transmission of Ranavirus between Ectothermic Vertebrate Hosts

    PubMed Central

    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. PMID:24667325

  14. 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

  15. Pyogenic Vertebral Osteomyelitis in Heroin Addicts

    PubMed Central

    Fishbach, Ronald S.; Rosenblatt, Jon E.; Dahlgren, James G.

    1973-01-01

    The diagnosis of pyogenic vertebral osteomyelitis was made in seven narcotic addicts between 1967 and 1972. Vertebrae involved were either cervical or lumbar. Bacteriologic diagnosis was made in each case by percutaneous needle biopsy and aspiration. Staphylococcus aureus was cultured in two patients. Five patients had infections due to Gram-negative bacteria, including Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacter. All patients were cured by treatment with antibiotics and immobilization. PMID:4199351

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. Journey to the skin: Somatosensory peripheral axon guidance and morphogenesis.

    PubMed

    Wang, Fang; Julien, Donald P; Sagasti, Alvaro

    2013-01-01

    The peripheral axons of vertebrate tactile somatosensory neurons travel long distances from ganglia just outside the central nervous system to the skin. Once in the skin these axons form elaborate terminals whose organization must be regionally patterned to detect and accurately localize different kinds of touch stimuli. This review describes key studies that identified choice points for somatosensory axon growth cones and the extrinsic molecular cues that function at each of those steps. While much has been learned in the past 20 years about the guidance of these axons, there is still much to be learned about how the peripheral axons of different kinds of somatosensory neurons adopt different trajectories and form specific terminal structures. PMID:23670092

  3. 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

  4. 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

  5. IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

    PubMed

    Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

    2016-02-01

    suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. © 2015 American Society for Bone and Mineral Research. PMID:26260312

  6. 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

  7. 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

  8. 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

  9. Regulation of epithelial morphogenesis by the G protein-coupled receptor mist and its ligand fog.

    PubMed

    Manning, Alyssa J; Peters, Kimberly A; Peifer, Mark; Rogers, Stephen L

    2013-11-12

    Epithelial morphogenesis is essential for shaping organs and tissues and for establishment of the three embryonic germ layers during gastrulation. Studies of gastrulation in Drosophila have provided insight into how epithelial morphogenesis is governed by developmental patterning mechanisms. We developed an assay to recapitulate morphogenetic shape changes in individual cultured cells and used RNA interference-based screening to identify Mist, a Drosophila G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) that transduces signals from the secreted ligand Folded gastrulation (Fog) in cultured cells. Mist functioned in Fog-dependent embryonic morphogenesis, and the transcription factor Snail regulated expression of mist in zygotes. Our data revealed how a cell fate transcriptional program acts through a ligand-GPCR pair to stimulate epithelial morphogenetic shape changes. PMID:24222713

  10. Regulation of Epithelial Morphogenesis by the G-Protein Coupled Receptor Mist and its Ligand Fog*

    PubMed Central

    Manning, Alyssa J.; Peters, Kimberly A.; Peifer, Mark; Rogers, Stephen L.

    2014-01-01

    Epithelial morphogenesis is essential for shaping organs and tissues and for establishment of the three embryonic germ layers during gastrulation. Studies of gastrulation in Drosophila have provided insight into how epithelial morphogenesis is governed by developmental patterning mechanisms. We developed an assay to recapitulate morphogenetic shape changes in individual cultured cells, and used RNAi-based screening to identify Mist, a Drosophila G protein-coupled receptor (GPCR) that transduces signals from the secreted ligand Folded gastrulation (Fog) in cultured cells. Mist functioned in Fog-dependent embryonic morphogenesis, and the transcription factor Snail regulated expression of mist in zygotes. Our data revealed how a cell fate transcriptional program acts through a ligand-GPCR pair to stimulate epithelial morphogenetic shape changes. PMID:24222713

  11. 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

  12. Prospective Single-Site Experience with Radiofrequency-Targeted Vertebral Augmentation for Osteoporotic Vertebral Compression Fracture

    PubMed Central

    Moser, Franklin G.; Maya, Marcel M.; Blaszkiewicz, Laura; Scicli, Andrea; Miller, Larry E.; Block, Jon E.

    2013-01-01

    Vertebral augmentation procedures are widely used to treat osteoporotic vertebral compression fractures (VCFs). We report our initial experience with radiofrequency-targeted vertebral augmentation (RF-TVA) in 20 patients aged 50 to 90 years with single-level, symptomatic osteoporotic VCF between T10 and L5, back pain severity > 4 on a 0 to 10 scale, Oswestry Disability Index ≥ 21%, 20% to 90% vertebral height loss compared to adjacent vertebral body, and fracture age < 6 months. After treatment, patients were followed through hospital discharge and returned for visits after 1 week, 1 month, and 3 months. Back pain severity improved 66% (P < 0.001), from 7.9 (95% CI: 7.1 to 8.6) at pretreatment to 2.7 (95% CI: 1.5 to 4.0) at 3 months. Back function improved 46% (P < 0.001), from 74 (95% CI: 69% to 79%) at pretreatment to 40 (95% CI: 33% to 47%) at 3 months. The percentage of patients regularly consuming pain medication was 70% at pretreatment and only 21% at 3 months. No adverse events related to the device or procedure were reported. RF-TVA reduces back pain severity, improves back function, and reduces pain medication requirements with no observed complications in patients with osteoporotic VCF. PMID:24228187

  13. The Petunia GRAS Transcription Factor ATA/RAM1 Regulates Symbiotic Gene Expression and Fungal Morphogenesis in Arbuscular Mycorrhiza1

    PubMed Central

    Rich, Mélanie K.

    2015-01-01

    Arbuscular mycorrhiza (AM) is a mutual symbiosis that involves a complex symbiotic interface over which nutrients are exchanged between the plant host and the AM fungus. Dozens of genes in the host are required for the establishment and functioning of the interaction, among them nutrient transporters that mediate the uptake of mineral nutrients delivered by the fungal arbuscules. We have isolated in a genetic mutant screen a petunia (Petunia hybrida) GIBBERELLIC ACID INSENSITIVE, REPRESSOR of GIBBERELLIC ACID INSENSITIVE, and SCARECROW (GRAS)-type transcription factor, ATYPICAL ARBUSCULE (ATA), that acts as the central regulator of AM-related genes and is required for the morphogenesis of arbuscules. Forced mycorrhizal inoculations from neighboring wild-type plants revealed an additional role of ATA in restricting mycorrhizal colonization of the root meristem. The lack of ATA, which represents the ortholog of REQUIRED FOR ARBUSCULAR MYCORRHIZA1 in Medicago truncatula, renders the interaction completely ineffective, hence demonstrating the central role of AM-related genes for arbuscule development and function. PMID:25971550

  14. 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

  15. 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

  16. Effect of fulvic acids on the electrolytes physiology in vertebrates

    NASA Astrophysics Data System (ADS)

    Morales, O. Y.; Navarrete, J. M.; Gracia, I.; Macias, L.; Rivera, M.; Sanchez, F.

    2011-10-01

    Fulvic acids are the active principle in humus fertilizers which are the cause of better absorption of mineral ions from soil to plant tissues. Tested in mice by making use of radioactive labeled ions, they showed their action of enhancing by a factor greater than two the filtration through liver of PO 43- and Ca 2+ from digestive tract to blood serum as well as through kidney from blood serum to urine. Following this research, Fe 3+ and I 1- ions labeled with 59Fe and 131I have been tested and reported in the present paper. Results showed that iron ions are completely fixed in red cells, with no residue eliminated by urine, while iodine ions are fixed in thyroid gland, with some residue eliminated by urine. Both ions were fixed in said tissues by factors larger than two when they are escorted by fulvic acids. A general distribution of these ions in blood, urine, feces, liver, kidney and thyroid gland has been surveyed, trying to find the earliest effect of fulvic acids in the physiology of vertebrates.

  17. 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.

  18. Plant Growth and Morphogenesis under Different Gravity Conditions: Relevance to Plant Life in Space.

    PubMed

    Hoson, Takayuki

    2014-01-01

    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. PMID:25370193

  19. Mammary fibroblasts regulate morphogenesis of normal and tumorigenic breast epithelial cells by mechanical and paracrine signals

    PubMed Central

    Lühr, Inke; Friedl, Andreas; Overath, Thorsten; Tholey, Andreas; Kunze, Thomas; Hilpert, Felix; Sebens, Susanne; Arnold, Norbert; Rösel, Frank; Oberg, Hans-Heinrich; Maass, Nicolai; Mundhenke, Christoph; Jonat, Walter; Bauer, Maret

    2013-01-01

    Stromal factors play a critical role in the development of the mammary gland. Using a three dimensional-coculture model we demonstrate a significant role for stromal fibroblasts in the regulation of normal mammary epithelial morphogenesis and the control of tumor growth. Both soluble factors secreted by fibroblasts and fibroblast-derived modifications of the matrix compliance contribute to the regulation of epithelial cell morphogenesis. Readjustment of matrix tension by fibroblasts can even induce a phenotypic reversion of breast carcinoma cells. These data offer a basis to develop new strategies for the normalization of the tumor stroma as an innovative target in cancer therapy. PMID:22776560

  20. 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

  1. Anthropometric measurements and vertebral deformities. European Vertebral Osteoporosis Study (EVOS) Group.

    PubMed

    Johnell, O; O'Neill, T; Felsenberg, D; Kanis, J; Cooper, C; Silman, A J

    1997-08-15

    To investigate the association between anthropometric indices and morphometrically determined vertebral deformity, the authors carried out a cross-sectional study using data from the European Vertebral Osteoporosis Study (EVOS), a population-based study of vertebral osteoporosis in 36 European centers from 19 countries. A total of 16,047 EVOS subjects were included in this analysis, of whom 1,973 subjects (915 males, 1,058 females) (12.3%) aged 50 years or over had one or more vertebral deformities ("cases"). The cases were compared with the 14,074 subjects (6,539 males, 7,535 females) with morphometrically normal spines ("controls"). Data were collected on self-reported height at age 25 years and minimum weight after age 25 years, as well as on current measured height and weight. Body mass index (BMI) and height and weight change were calculated from these data. The relations between these variables and vertebral deformity were examined separately by sex with logistic regression adjusting for age, smoking, and physical activity. In females, there was a significant trend of decreasing risk with increasing quintile of current weight, current BMI, and weight gain since age 25 years. In males, subjects in the lightest quintile for these measures were at increased risk but there was no evidence of a trend. An ecologic analysis by country revealed a negative correlation between mean BMI and the prevalence of deformity in females but not in males. The authors conclude that low body weight is associated with presence of vertebral deformity. PMID:9270407

  2. 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

  3. Dynamic Analysis of Vascular Morphogenesis Using Transgenic Quail Embryos

    PubMed Central

    Huss, David; Filla, Michael B.; Czirok, Andras; Rongish, Brenda J.; Little, Charles D.; Fraser, Scott E.; Lansford, Rusty

    2010-01-01

    Background One of the least understood and most central questions confronting biologists is how initially simple clusters or sheet-like cell collectives can assemble into highly complex three-dimensional functional tissues and organs. Due to the limits of oxygen diffusion, blood vessels are an essential and ubiquitous presence in all amniote tissues and organs. Vasculogenesis, the de novo self-assembly of endothelial cell (EC) precursors into endothelial tubes, is the first step in blood vessel formation [1]. Static imaging and in vitro models are wholly inadequate to capture many aspects of vascular pattern formation in vivo, because vasculogenesis involves dynamic changes of the endothelial cells and of the forming blood vessels, in an embryo that is changing size and shape. Methodology/Principal Findings We have generated Tie1 transgenic quail lines Tg(tie1:H2B-eYFP) that express H2B-eYFP in all of their endothelial cells which permit investigations into early embryonic vascular morphogenesis with unprecedented clarity and insight. By combining the power of molecular genetics with the elegance of dynamic imaging, we follow the precise patterning of endothelial cells in space and time. We show that during vasculogenesis within the vascular plexus, ECs move independently to form the rudiments of blood vessels, all while collectively moving with gastrulating tissues that flow toward the embryo midline. The aortae are a composite of somatic derived ECs forming its dorsal regions and the splanchnic derived ECs forming its ventral region. The ECs in the dorsal regions of the forming aortae exhibit variable mediolateral motions as they move rostrally; those in more ventral regions show significant lateral-to-medial movement as they course rostrally. Conclusions/Significance The present results offer a powerful approach to the major challenge of studying the relative role(s) of the mechanical, molecular, and cellular mechanisms of vascular development. In past studies

  4. Putative functions of extracellular matrix glycoproteins in secondary palate morphogenesis

    PubMed Central

    d'Amaro, Rocca; Scheidegger, Rolf; Blumer, Susan; Pazera, Pawel; Katsaros, Christos; Graf, Daniel; Chiquet, Matthias

    2012-01-01

    Cleft palate is a common birth defect in humans. Elevation and fusion of paired palatal shelves are coordinated by growth and transcription factors, and mutations in these can cause malformations. Among the effector genes for growth factor signaling are extracellular matrix (ECM) glycoproteins. These provide substrates for cell adhesion (e.g., fibronectin, tenascins), but also regulate growth factor availability (e.g., fibrillins). Cleft palate in Bmp7 null mouse embryos is caused by a delay in palatal shelf elevation. In contrast, palatal shelves of Tgf-β3 knockout mice elevate normally, but a cleft develops due to their failure to fuse. However, nothing is known about a possible functional interaction between specific ECM proteins and Tgf-β/Bmp family members in palatogenesis. To start addressing this question, we studied the mRNA and protein distribution of relevant ECM components during secondary palate development, and compared it to growth factor expression in wildtypewild type and mutant mice. We found that fibrillin-2 (but not fibrillin-1) mRNA appeared in the mesenchyme of elevated palatal shelves adjacent to the midline epithelial cells, which were positive for Tgf-β3 mRNA. Moreover, midline epithelial cells started expressing fibronectin upon contact of the two palatal shelves. These findings support the hypothesis that fibrillin-2 and fibronectin are involved in regulating the activity of Tgf-β3 at the fusing midline. In addition, we observed that tenascin-W (but not tenascin-C) was misexpressed in palatal shelves of Bmp7-deficient mouse embryos. In contrast to tenascin-C, tenascin-W secretion was strongly induced by Bmp7 in embryonic cranial fibroblasts in vitro. These results are consistent with a putative function for tenascin-W as a target of Bmp7 signaling during palate elevation. Our results indicate that distinct ECM proteins are important for morphogenesis of the secondary palate, both as downstream effectors and as regulators of Tgf

  5. Putative functions of extracellular matrix glycoproteins in secondary palate morphogenesis.

    PubMed

    d'Amaro, Rocca; Scheidegger, Rolf; Blumer, Susan; Pazera, Pawel; Katsaros, Christos; Graf, Daniel; Chiquet, Matthias

    2012-01-01

    Cleft palate is a common birth defect in humans. Elevation and fusion of paired palatal shelves are coordinated by growth and transcription factors, and mutations in these can cause malformations. Among the effector genes for growth factor signaling are extracellular matrix (ECM) glycoproteins. These provide substrates for cell adhesion (e.g., fibronectin, tenascins), but also regulate growth factor availability (e.g., fibrillins). Cleft palate in Bmp7 null mouse embryos is caused by a delay in palatal shelf elevation. In contrast, palatal shelves of Tgf-β3 knockout mice elevate normally, but a cleft develops due to their failure to fuse. However, nothing is known about a possible functional interaction between specific ECM proteins and Tgf-β/Bmp family members in palatogenesis. To start addressing this question, we studied the mRNA and protein distribution of relevant ECM components during secondary palate development, and compared it to growth factor expression in wildtypewild type and mutant mice. We found that fibrillin-2 (but not fibrillin-1) mRNA appeared in the mesenchyme of elevated palatal shelves adjacent to the midline epithelial cells, which were positive for Tgf-β3 mRNA. Moreover, midline epithelial cells started expressing fibronectin upon contact of the two palatal shelves. These findings support the hypothesis that fibrillin-2 and fibronectin are involved in regulating the activity of Tgf-β3 at the fusing midline. In addition, we observed that tenascin-W (but not tenascin-C) was misexpressed in palatal shelves of Bmp7-deficient mouse embryos. In contrast to tenascin-C, tenascin-W secretion was strongly induced by Bmp7 in embryonic cranial fibroblasts in vitro. These results are consistent with a putative function for tenascin-W as a target of Bmp7 signaling during palate elevation. Our results indicate that distinct ECM proteins are important for morphogenesis of the secondary palate, both as downstream effectors and as regulators of Tgf

  6. Wnt-7a in feather morphogenesis: involvement of anterior-posterior asymmetry and proximal-distal elongation demonstrated with an in vitro reconstitution model.

    PubMed

    Widelitz, R B; Jiang, T X; Chen, C W; Stott, N S; Jung, H S; Chuong, C M

    1999-06-01

    How do vertebrate epithelial appendages form from the flat epithelia? Following the formation of feather placodes, the previously radially symmetrical primordia become anterior-posterior (A-P) asymmetrical and develop a proximo-distal (P-D) axis. Analysis of the molecular heterogeneity revealed a surprising parallel of molecular profiles in the A-P feather buds and the ventral-dorsal (V-D) Drosophila appendage imaginal discs. The functional significance was tested with an in vitro feather reconstitution model. Wnt-7a expression initiated all over the feather tract epithelium, intensifying as it became restricted first to the primordia domain, then to an accentuated ring pattern within the primordia border, and finally to the posterior bud. In contrast, sonic hedgehog expression was induced later as a dot within the primordia. RCAS was used to overexpress Wnt-7a in reconstituted feather explants derived from stage 29 dorsal skin to further test its function in feather formation. Control skin formed normal elongated, slender buds with A-P orientation, but Wnt-7a overexpression led to plateau-like skin appendages lacking an A-P axis. Feathers in the Wnt-7a overexpressing skin also had inhibited elongation of the P-D axes. This was not due to a lack of cell proliferation, which actually was increased although randomly distributed. While morphogenesis was perturbed, differentiation proceeded as indicated by the formation of barb ridges. Wnt-7a buds have reduced expression of anterior (Tenascin) bud markers. Middle (Notch-1) and posterior bud markers including Delta-1 and Serrate-1 were diffusely expressed. The results showed that ectopic Wnt-7a expression enhanced properties characteristic of the middle and posterior feather buds and suggest that P-D elongation of vertebrate skin appendages requires balanced interactions between the anterior and posterior buds. PMID:10331970

  7. 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.

  8. 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

  9. 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

  10. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance.

    PubMed

    Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

    2015-01-01

    Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80-11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density. PMID:26314987

  11. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance

    PubMed Central

    Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

    2015-01-01

    Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80–11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density. PMID:26314987

  12. Histology and affinity of anaspids, and the early evolution of the vertebrate dermal skeleton.

    PubMed

    Keating, Joseph N; Donoghue, Philip C J

    2016-03-16

    The assembly of the gnathostome bodyplan constitutes a formative episode in vertebrate evolutionary history, an interval in which the mineralized skeleton and its canonical suite of cell and tissue types originated. Fossil jawless fishes, assigned to the gnathostome stem-lineage, provide an unparalleled insight into the origin and evolution of the skeleton, hindered only by uncertainty over the phylogenetic position and evolutionary significance of key clades. Chief among these are the jawless anaspids, whose skeletal composition, a rich source of phylogenetic information, is poorly characterized. Here we survey the histology of representatives spanning anaspid diversity and infer their generalized skeletal architecture. The anaspid dermal skeleton is composed of odontodes comprising spheritic dentine and enameloid, overlying a basal layer of acellular parallel fibre bone containing an extensive shallow canal network. A recoded and revised phylogenetic analysis using equal and implied weights parsimony resolves anaspids as monophyletic, nested among stem-gnathostomes. Our results suggest the anaspid dermal skeleton is a degenerate derivative of a histologically more complex ancestral vertebrate skeleton, rather than reflecting primitive simplicity. Hypotheses that anaspids are ancestral skeletonizing lampreys, or a derived lineage of jawless vertebrates with paired fins, are rejected. PMID:26962140

  13. Histology and affinity of anaspids, and the early evolution of the vertebrate dermal skeleton

    PubMed Central

    Keating, Joseph N.; Donoghue, Philip C. J.

    2016-01-01

    The assembly of the gnathostome bodyplan constitutes a formative episode in vertebrate evolutionary history, an interval in which the mineralized skeleton and its canonical suite of cell and tissue types originated. Fossil jawless fishes, assigned to the gnathostome stem-lineage, provide an unparalleled insight into the origin and evolution of the skeleton, hindered only by uncertainty over the phylogenetic position and evolutionary significance of key clades. Chief among these are the jawless anaspids, whose skeletal composition, a rich source of phylogenetic information, is poorly characterized. Here we survey the histology of representatives spanning anaspid diversity and infer their generalized skeletal architecture. The anaspid dermal skeleton is composed of odontodes comprising spheritic dentine and enameloid, overlying a basal layer of acellular parallel fibre bone containing an extensive shallow canal network. A recoded and revised phylogenetic analysis using equal and implied weights parsimony resolves anaspids as monophyletic, nested among stem-gnathostomes. Our results suggest the anaspid dermal skeleton is a degenerate derivative of a histologically more complex ancestral vertebrate skeleton, rather than reflecting primitive simplicity. Hypotheses that anaspids are ancestral skeletonizing lampreys, or a derived lineage of jawless vertebrates with paired fins, are rejected. PMID:26962140

  14. Vertebrate gravity sensors as dynamic systems

    NASA Technical Reports Server (NTRS)

    Ross, M. D.

    1985-01-01

    This paper considers verterbrate gravity receptors as dynamic sensors. That is, it is hypothesized that gravity is a constant force to which an acceleration-sensing system would readily adapt. Premises are considered in light of the presence of kinocilia on hair cells of vertebrate gravity sensors; differences in loading of the sensors among species; and of possible reduction in loading by inclusion of much organic material in otoconia. Moreover, organic-inorganic interfaces may confer a piezoelectric property upon otoconia, which increase the sensitivity of the sensory system to small accelerations. Comparisons with man-made accelerometers are briefly taken up.

  15. 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.

  16. 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

  17. Pullout strength of anterior spinal instrumentation: a product comparison of seven screws in calf vertebral bodies

    PubMed Central

    Wahl, Dieter; Wild, Alexander; Krauspe, Rüdiger; Schneider, Erich; Linke, Berend

    2007-01-01

    A lot of new implant devices for spine surgery are coming onto the market, in which vertebral screws play a fundamental role. The new screws developed for surgery of spine deformities have to be compared to established systems. A biomechanical in vitro study was designed to assess the bone–screw interface fixation strength of seven different screws used for correction of scoliosis in spine surgery. The objectives of the current study were twofold: (1) to evaluate the initial strength at the bone–screw interface of newly developed vertebral screws (Universal Spine System II) compared to established systems (product comparison) and (2) to evaluate the influence of screw design, screw diameter, screw length and bone mineral density on pullout strength. Fifty-six calf vertebral bodies were instrumented with seven different screws (USS II anterior 8.0 mm, USS II posterior 6.2 mm, KASS 6.25 mm, USS II anterior 6.2 mm, USS II posterior 5.2 mm, USS 6.0 mm, USS 5.0 mm). Bone mineral density (BMD) was determined by quantitative computed tomography (QCT). Failure in axial pullout was tested using a displacement-controlled universal test machine. USS II anterior 8.0 mm showed higher pullout strength than all other screws. The difference constituted a tendency (P = 0.108) when compared to USS II posterior 6.2 mm (+19%) and was significant in comparison to the other screws (+30 to +55%, P < 0.002). USS II posterior 6.2 mm showed significantly higher pullout strength than USS 5.0 mm (+30%, P = 0.014). The other screws did not differ significantly in pullout strength. Pullout strength correlated significantly with BMD (P = 0.0015) and vertebral body width/screw length (P < 0.001). The newly developed screws for spine surgery (USS II) show higher pullout strength when compared to established systems. Screw design had no significant influence on pullout force in vertebral body screws, but outer diameter of the screw, screw length and BMD are good predictors

  18. A kind of specific osteolytic destruction of the vertebral bodies

    PubMed Central

    Peng, Baogan; Chen, Jinhong; Pang, Xiaodong; Hei, Yan

    2012-01-01

    This report describes two young patients with osteolytic destruction in two adjacent vertebral bodies along with the intervertebral disc, and reveals its possible mechanism. A lateral radiograph and CT scan displayed a giant osteolytic cavity in the L4 vertebral body. An MRI or CT scan with a two-dimensional reconstruction displayed the same changes in the L4 vertebral body and lower endplate erosion in the L3 vertebral body. A comprehensive preoperative evaluation did not identify a specific cause of vertebral destruction. Both patients underwent anterior lumbar fusion surgery. The lesions were removed for histological and immunohistochemical examination. Histopathological study of the destructed vertebral bodies in the two patients revealed the disruption or atrophy of bone trabeculae with infiltration of a large amount of B-lymphocytes and macrophages into the marrow cavities. Studies of its pathogenesis reveal that it is likely to be a B-lymphocyte-mediated local immune inflammatory reaction in the lumbar spine. PMID:22675148

  19. Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis

    PubMed Central

    Harel, Itamar; Maezawa, Yoshiro; Avraham, Roi; Rinon, Ariel; Ma, Hsiao-Yen; Cross, Joe W.; Leviatan, Noam; Hegesh, Julius; Roy, Achira; Jacob-Hirsch, Jasmine; Rechavi, Gideon; Carvajal, Jaime; Tole, Shubha; Kioussi, Chrissa; Quaggin, Susan; Tzahor, Eldad

    2012-01-01

    The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects. PMID:23112163

  20. Integration of the transcriptional networks regulating limb morphogenesis.

    PubMed

    Rabinowitz, Adam H; Vokes, Steven A

    2012-08-15

    The developing limb is one of the best described vertebrate systems for understanding how coordinated gene expression during embryogenesis leads to the structures present in the mature organism. This knowledge, derived from decades of research, is largely based upon gain- and loss-of-function experiments. These studies have provided limited information about how the key signaling pathways interact with each other and the downstream effectors of these pathways. We summarize our current understanding of known genetic interactions in the context of three temporally defined gene regulatory networks. These networks crystallize our current knowledge, depicting a dynamic process involving multiple feedback loops between the ectoderm and mesoderm. At the same time, they highlight the fact that many essential processes are still largely undescribed. Much of the dynamic transcriptional activity occurring during development is regulated by distal cis-regulatory elements. Modern genomic tools have provided new approaches for studying the function of cis-regulatory elements and we discuss the results of these studies in regard to understanding limb development. Ultimately, these genomic techniques will allow scientists to understand how multiple signaling pathways are integrated in space and time to drive gene expression and regulate the formation of the limb. PMID:22683377

  1. The SCPP gene family and the complexity of hard tissues in vertebrates.

    PubMed

    Kawasaki, Kazuhiko

    2011-01-01

    Diverse hard tissues constituted a tooth-like skeletal element in extinct jawless vertebrates. Today, similar tissues are found in our teeth. These tissues mineralize in the extracellular matrix and involve various macromolecules. Among these molecules are secretory calcium-binding phosphoproteins (SCPPs) coded by genes that arose by duplication. Although the repertoire of SCPPs may vary in different lineages, some SCPPs are unusually acidic and are thought to participate in the mineralization of a collagenous matrix, principally either bone or dentin. Other SCPPs are rich in Pro and Gln (P/Q) and are employed to form the tooth surface. In tetrapods, the tooth surface is usually covered with enamel which develops in a matrix comprised of P/Q-rich SCPPs. By contrast, the tooth surface tissue in teleosts is called enameloid and it forms in a dentin-like collagenous matrix. Despite the difference in their matrix, both enamel and enameloid mature into hypermineralized inorganic tissues. Notably, some P/Q-rich SCPP genes are primarily expressed at this stage and their proteins localize between the tooth surface and overlying dental epithelium. Moreover, an orthologous gene is used for maturation of these 2 different tissues. These findings suggest distinct roles of acidic and P/Q-rich SCPPs during the evolution of hard tissues. Acidic SCPPs initially regulated the mineralization of bone, dentin, or a similar ancient collagenous tissue through interaction with calcium ions. P/Q-rich SCPPs arose next and originally assembled a structure or a space that facilitated the hypermineralization of dentin or a dentin-like tissue. Subsequently, some P/Q-rich SCPPs were coopted for the mineralizing enamel matrix. More recently, however, many SCPP genes were lost in toothless birds and mammals. Thus, it appears that, in vertebrates, the phenotypic complexity of hard tissues correlates with gain and loss of SCPP genes. PMID:21576905

  2. A critical role for NF2 and the Hippo pathway in branching morphogenesis.

    PubMed

    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. Regulation of Neuronal Morphogenesis and Positioning by Ubiquitin-Specific Proteases in the Cerebellum

    PubMed Central

    Anckar, Julius; Bonni, Azad

    2015-01-01

    Ubiquitin signaling mechanisms play fundamental roles in the cell-intrinsic control of neuronal morphogenesis and connectivity in the brain. However, whereas specific ubiquitin ligases have been implicated in key steps of neural circuit assembly, the roles of ubiquitin-specific proteases (USPs) in the establishment of neuronal connectivity have remained unexplored. Here, we report a comprehensive analysis of USP family members in granule neuron morphogenesis and positioning in the rodent cerebellum. We identify a set of 32 USPs that are expressed in granule neurons. We also characterize the subcellular localization of the 32 USPs in granule neurons using a library of expression plasmids encoding GFP-USPs. In RNAi screens of the 32 neuronally expressed USPs, we uncover novel functions for USP1, USP4, and USP20 in the morphogenesis of granule neuron dendrites and axons and we identify a requirement for USP30 and USP33 in granule neuron migration in the rodent cerebellar cortex in vivo. These studies reveal that specific USPs with distinct spatial localizations harbor key functions in the control of neuronal morphogenesis and positioning in the mammalian cerebellum, with important implications for our understanding of the cell-intrinsic mechanisms that govern neural circuit assembly in the brain. PMID:25607801

  4. Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis

    PubMed Central

    Rodríguez-Fraticelli, Alejo E.; Auzan, Muriel; Alonso, Miguel A.; Bornens, Michel

    2012-01-01

    Epithelial organ morphogenesis involves sequential acquisition of apicobasal polarity by epithelial cells and development of a functional lumen. In vivo, cells perceive signals from components of the extracellular matrix (ECM), such as laminin and collagens, as well as sense physical conditions, such as matrix stiffness and cell confinement. Alteration of the mechanical properties of the ECM has been shown to promote cell migration and invasion in cancer cells, but the effects on epithelial morphogenesis have not been characterized. We analyzed the effects of cell confinement on lumen morphogenesis using a novel, micropatterned, three-dimensional (3D) Madin-Darby canine kidney cell culture method. We show that cell confinement, by controlling cell spreading, limits peripheral actin contractility and promotes centrosome positioning and lumen initiation after the first cell division. In addition, peripheral actin contractility is mediated by master kinase Par-4/LKB1 via the RhoA–Rho kinase–myosin II pathway, and inhibition of this pathway restores lumen initiation in minimally confined cells. We conclude that cell confinement controls nuclear–centrosomal orientation and lumen initiation during 3D epithelial morphogenesis. PMID:22965908

  5. 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

  6. Development of gene-tagged SNP markers for gland morphogenesis in cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cotton (Gossypium spp.) plants, including cottonseed, have small, pigmented glands containing gossypol and other terpenoid compounds that are toxic to humans and non-ruminant animals. Single nucleotide polymorphism (SNP) markers involved in gland morphogenesis are useful for the discovery of candid...

  7. ULTRA-HIGH CO2 LEVELS ENHANCE LOBLOLLY PINE SEEDLING GROWTH, MORPHOGENESIS, AND SECONDARY METABOLISM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The growth (fresh weight), morphogenesis (number of needles, roots, and shoot length), and monoterpene (alpha- and beta-pinene) levels of Pinus taeda L. (loblolly pine) seedlings were determined under 350, 1,500, 3,000, 10,000, or 30,000 umol mol**-1 CO2 after 30 days incubation under greenhouse con...

  8. Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis

    NASA Astrophysics Data System (ADS)

    Castelli, Maddalena; Boca, Manila; Chiaravalli, Marco; Ramalingam, Harini; Rowe, Isaline; Distefano, Gianfranco; Carroll, Thomas; Boletta, Alessandra

    2013-10-01

    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.

  9. 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

  10. TECHNIQUES TO IMPROVE GROWTH, MORPHOGENESIS, AND SECONDARY METABOLISM RESPONSES FROM LAMIACEAE SPECIES IN VITRO

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cultural procedures to improve growth (fresh weight) and morphogenesis (leaves, shoots, and roots) responses from mint family (Lamiaceae) species (e.g., basil, catnip, oregano, and spearmint) in vitro are presented. Novel plant tissue culture systems were employed to increase biomass and shooting. ...

  11. 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

  12. Geranylgeranyl Diphosphate Synthase Modulates Fetal Lung Branching Morphogenesis Possibly through Controlling K-Ras Prenylation.

    PubMed

    Jia, Wen-Jun; Jiang, Shan; Tang, Qiao-Li; Shen, Di; Xue, Bin; Ning, Wen; Li, Chao-Jun

    2016-06-01

    G proteins play essential roles in regulating fetal lung development, and any defects in their expression or function (eg, activation or posttranslational modification) can lead to lung developmental malformation. Geranylgeranyl diphosphate synthase (GGPPS) can modulate protein prenylation that is required for protein membrane-anchoring and activation. Here, we report that GGPPS regulates fetal lung branching morphogenesis possibly through controlling K-Ras prenylation during fetal lung development. GGPPS was continuously expressed in lung epithelium throughout whole fetal lung development. Specific deletion of geranylgeranyl diphosphate synthase 1 (Ggps1) in lung epithelium during fetal lung development resulted in neonatal respiratory distress syndrome-like disease. The knockout mice died at postnatal day 1 of respiratory failure, and the lungs showed compensatory pneumonectasis, pulmonary atelectasis, and hyaline membranes. Subsequently, we proved that lung malformations in Ggps1-deficient mice resulted from the failure of fetal lung branching morphogenesis. Further investigation revealed Ggps1 deletion blocked K-Ras geranylgeranylation and extracellular signal-related kinase 1 or 2/mitogen-activated protein kinase signaling, which in turn disturbed fibroblast growth factor 10 regulation on fetal lung branching morphogenesis. Collectively, our data suggest that GGPPS is essential for maintaining fetal lung branching morphogenesis, which is possibly through regulating K-Ras prenylation. PMID:27106761

  13. The Vertebrate Primary Cilium in Development, Homeostasis, and Disease

    PubMed Central

    Gerdes, Jantje M.; Davis, Erica E.; Katsanis, Nicholas

    2010-01-01

    Cilia are complex structures that have garnered interest because of their roles in vertebrate development and their involvement in human genetic disorders. In contrast to multicellular invertebrates in which cilia are restricted to specific cell types, these organelles are found almost ubiquitously in vertebrate cells, where they serve a diverse set of signaling functions. Here, we highlight properties of vertebrate cilia, with particular emphasis on their relationship with other subcellular structures, and explore the physiological consequences of ciliary dysfunction. PMID:19345185

  14. DISTORTED3/SCAR2 is a putative arabidopsis WAVE complex subunit that activates the Arp2/3 complex and is required for epidermal morphogenesis.

    PubMed

    Basu, Dipanwita; Le, Jie; El-Essal, Salah El-Din; Huang, Shanjin; Zhang, Chunhua; Mallery, Eileen L; Koliantz, Gregore; Staiger, Christopher J; Szymanski, Daniel B

    2005-02-01

    In a plant cell, a subset of actin filaments function as a scaffold that positions the endomembrane system and acts as a substrate on which organelle motility occurs. Other actin filament arrays appear to be more dynamic and reorganize in response to growth signals and external cues. The distorted group of trichome morphology mutants provides powerful genetic tools to study the control of actin filament nucleation in the context of morphogenesis. In this article, we report that DISTORTED3 (DIS3) encodes a plant-specific SCAR/WAVE homolog. Null alleles of DIS3, like those of other Arabidopsis thaliana WAVE and Actin-Related Protein (ARP) 2/3 subunit genes, cause trichome distortion, defects in cell-cell adhesion, and reduced hypocotyl growth in etiolated seedlings. DIS3 efficiently activates the actin filament nucleation and branching activity of vertebrate Arp2/3 and functions within a WAVE-ARP2/3 pathway in vivo. DIS3 may assemble into a WAVE complex via a physical interaction with a highly diverged Arabidopsis Abi-1-like bridging protein. These results demonstrate the utility of the Arabidopsis trichome system to understand how the WAVE and ARP2/3 complexes translate signaling inputs into a coordinated morphogenetic response. PMID:15659634

  15. 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

  16. Vertebrate helentrons and other novel Helitrons.

    PubMed

    Poulter, Russell T M; Goodwin, Timothy J D; Butler, Margaret I

    2003-08-14

    Helitrons, a novel class of eukaryote mobile genetic elements, are distinguished from other transposable elements by encoding a 'rolling circle' replication (RCR) protein (Rep) and a helicase. Helitrons have recently been described from Arabidopsis, rice and the nematode Caenorhabditis. We now report the discovery of Helitron-like elements in vertebrates, specifically in the genomes of the fish Danio rerio and Sphoeroides nephelus. We also describe Helitrons from the white rot fungus Phanerochaete chrysosporium and from the Anopheles genome. Many of the fish Helitrons have an uncorrupted open reading frame encoding both the RCR Rep protein and a helicase. These fish elements are of particular interest because they also encode, within the single open reading frame, an apurinic-apyrimidinic (AP) endonuclease most closely related to those of certain non-long terminal repeat retrotransposons. As they invariably carry an endonuclease and also form a very distinct clade, we have named these vertebrate elements 'helentrons'. It is likely that these helentrons are still active. PMID:12957391

  17. Degenerative diseases of the vertebral column.

    PubMed

    Resnick, D

    1985-07-01

    Several distinct degenerative processes affect the articulations of the vertebral column; each is associated with characteristic radiographic and pathologic abnormalities, and many are accompanied by significant clinical manifestations. A discussion of these processes is best accomplished according to the type of joint that is involved. With regard to cartilaginous articulations, of which the intervertebral disk is most important, intervertebral (osteo)chondrosis, spondylosis deformans, and, in the cervical spine, uncovertebral arthrosis are the major degenerative disorders. Osteoarthritis (osteoarthrosis) affects any of the synovium-lined joints of the vertebral column, including the apophyseal, costovertebral, transitional lumbosacral, median atlantoaxial, and sacroiliac articulations. Fibrous articulations, ligaments, or entheses (sites of tendon or ligament attachment to bone) are involved in diffuse idiopathic skeletal hyperostosis, ossification of the posterior spinal ligaments, and Baastrup disease. Of the many complications of these degenerative processes, alignment abnormalities (including segmental instability, degenerative spondylolisthesis, senile kyphosis, and degenerative scoliosis), intervertebral disk displacement, calcification or ossification, and spinal stenosis are the most important. PMID:3923556

  18. 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

  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. 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.

  1. The origins and evolution of vertebrate metamorphosis.

    PubMed

    Laudet, Vincent

    2011-09-27

    Metamorphosis, classically defined as a spectacular post-embryonic transition, is well exemplified by the transformation of a tadpole into a frog. It implies the appearance of new body parts (such as the limbs), the resorption of larval features (such as the tail) and the remodelling of many organs (such as the skin or the intestine). In vertebrates, metamorphosis has been well characterized in anuran amphibians, where thyroid hormones orchestrate the intricate and seemingly contradictory changes observed at the cellular and tissue levels. Thyroid hormones control a complex hierarchical cascade of target genes via binding to specific receptors, TRα and TRβ, ligand-activated transcription factors belonging to the nuclear receptor superfamily. Metamorphosis is actually widespread in the vertebrates, though quite diverse in the way it manifests in a particular species. Furthermore, evolutionary and ecological variations of this key event, from paedomorphosis to direct development, provide an excellent illustration of how tinkering with a control pathway can lead to divergent life histories. The study of invertebrate chordates has also shed light on the origin of metamorphosis. The available data suggest that post-embryonic remodelling governed by thyroid hormones is an ancestral feature of chordates. According to this view, metamorphosis of the anurans is an extreme example of a widespread life history transition. PMID:21959163

  2. 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.

  3. Recursive splicing in long vertebrate genes

    PubMed Central

    Blazquez, Lorea; Faro, Ana; Haberman, Nejc; Briese, Michael; Trabzuni, Daniah; Ryten, Mina; Weale, Michael E; Hardy, John; Modic, Miha; Curk, Tomaž; Wilson, Stephen W; Plagnol, Vincent; Ule, Jernej

    2015-01-01

    It is generally believed that splicing removes introns as single units from pre-mRNA transcripts. However, some long D. melanogaster introns contain a cryptic site, called a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing1,2. The extent to which recursive splicing occurs in other species and its mechanistic basis remain unclear. Here we identify highly conserved RS-sites in genes expressed in the mammalian brain that encode proteins functioning in neuronal development. Moreover, the RS-sites are found in some of the longest introns across vertebrates. We find that vertebrate recursive splicing requires initial definition of a “RS-exon” that follows the RS-site. The RS-exon is then excluded from the dominant mRNA isoform due to competition with a reconstituted 5′ splice site formed at the RS-site after the first splicing step. Conversely, the RS-exon is included when preceded by cryptic exons or promoters that are prevalent in long introns, but which fail to reconstitute an efficient 5′ splice site. Most RS-exons contain a premature stop codon such that their inclusion may decrease mRNA stability. Thus, by establishing a binary splicing switch, RS-sites demarcate different mRNA isoforms emerging from long genes by coupling inclusion of cryptic elements with RS-exons. PMID:25970246

  4. Recursive splicing in long vertebrate genes.

    PubMed

    Sibley, Christopher R; Emmett, Warren; Blazquez, Lorea; Faro, Ana; Haberman, Nejc; Briese, Michael; Trabzuni, Daniah; Ryten, Mina; Weale, Michael E; Hardy, John; Modic, Miha; Curk, Tomaž; Wilson, Stephen W; Plagnol, Vincent; Ule, Jernej

    2015-05-21

    It is generally believed that splicing removes introns as single units from precursor messenger RNA transcripts. However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing. The extent to which recursive splicing occurs in other species and its mechanistic basis have not been examined. Here we identify highly conserved RS-sites in genes expressed in the mammalian brain that encode proteins functioning in neuronal development. Moreover, the RS-sites are found in some of the longest introns across vertebrates. We find that vertebrate recursive splicing requires initial definition of an 'RS-exon' that follows the RS-site. The RS-exon is then excluded from the dominant mRNA isoform owing to competition with a reconstituted 5' splice site formed at the RS-site after the first splicing step. Conversely, the RS-exon is included when preceded by cryptic promoters or exons that fail to reconstitute an efficient 5' splice site. Most RS-exons contain a premature stop codon such that their inclusion can decrease mRNA stability. Thus, by establishing a binary splicing switch, RS-sites demarcate different mRNA isoforms emerging from long genes by coupling cryptic elements with inclusion of RS-exons. PMID:25970246

  5. 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

  6. 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

  7. Neural induction and early patterning in vertebrates.

    PubMed

    Ozair, Mohammad Zeeshan; Kintner, Chris; Brivanlou, Ali H

    2013-07-01

    In vertebrates, the development of the nervous system is triggered by signals from a powerful 'organizing' region of the early embryo during gastrulation. This phenomenon--neural induction--was originally discovered and given conceptual definition by experimental embryologists working with amphibian embryos. Work on the molecular circuitry underlying neural induction, also in the same model system, demonstrated that elimination of ongoing transforming growth factor-β (TGFβ) signaling in the ectoderm is the hallmark of anterior neural-fate acquisition. This observation is the basis of the 'default' model of neural induction. Endogenous neural inducers are secreted proteins that act to inhibit TGFβ ligands in the dorsal ectoderm. In the ventral ectoderm, where the signaling ligands escape the inhibitors, a non-neural fate is induced. Inhibition of the TGFβ pathway has now been demonstrated to be sufficient to directly induce neural fate in mammalian embryos as well as pluripotent mouse and human embryonic stem cells. Hence the molecular process that delineates neural from non-neural ectoderm is conserved across a broad range of organisms in the evolutionary tree. The availability of embryonic stem cells from mouse, primates, and humans will facilitate further understanding of the role of signaling pathways and their downstream mediators in neural induction in vertebrate embryos. PMID:24014419

  8. 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. PMID:25959851

  9. TRPM7 regulates gastrulation during vertebrate embryogenesis

    PubMed Central

    Liu, Wei; Su, Li-Ting; Khadka, Deepak K.; Mezzacappa, Courtney; Komiya, Yuko; Sato, Akira; Habas, Raymond; Runnels, Loren W.

    2010-01-01

    During gastrulation, cells in the dorsal marginal zone polarize, elongate, align and intercalate to establish the physical body axis of the developing embryo. Here we demonstrate that the bifunctional channel-kinase TRPM7 is specifically required for vertebrate gastrulation. TRPM7 is temporally expressed maternally and throughout development, and is spatially enriched in tissues undergoing convergent extension during gastrulation. Functional studies reveal that TRPM7’s ion channel, but not its kinase, specifically affects cell polarity and convergent extension movements during gastrulation, independent of mesodermal specification. During gastrulation, the non-canonical Wnt pathway via Dishevelled (Dvl) orchestrates the activities of the GTPases Rho and Rac to control convergent extension movements. We find that TRPM7 functions synergistically with non-canonical Wnt signaling to regulate Rac activity. The phenotype caused by depletion of the Ca2+- and Mg2+-permeant TRPM7 is suppressed by expression of a dominant negative form of Rac, as well as by Mg2+ supplementation or by expression of the Mg2+ transporter SLC41A2. Together, these studies demonstrate an essential role for the ion channel TRPM7 and Mg2+ in Rac-dependent polarized cell movements during vertebrate gastrulation. PMID:21145885

  10. Dominance in vertebrate broods and litters.

    PubMed

    Drummond, Hugh

    2006-03-01

    Drawing on the concepts and theory of dominance in adult vertebrates, this article categorizes the relationships of dominance between infant siblings, identifies the behavioral mechanisms that give rise to those relationships, and proposes a model to explain their evolution. Dominance relationships in avian broods can be classified according to the agonistic roles of dominants and subordinates as "aggression-submission," "aggression-resistance," "aggression-aggression," "aggression-avoidance," "rotating dominance," and "flock dominance." These relationships differ mainly in the submissiveness/pugnacity of subordinates, which is pivotal, and in the specificity/generality of the learning processes that underlie them. As in the dominance hierarchies of adult vertebrates, agonistic roles are engendered and maintained by several mechanisms, including differential fighting ability, assessment, trained winning and losing (especially in altricial species), learned individual relationships (especially in precocial species), site-specific learning, and probably group-level effects. An evolutionary framework in which the species-typical dominance relationship is determined by feeding mode, confinement, cost of subordination, and capacity for individual recognition, can be extended to mammalian litters and account for the aggression-submission and aggression-resistance observed in distinct populations of spotted hyenas and the "site-specific dominance" (teat ownership) of some pigs, felids, and hyraxes. Little is known about agonism in the litters of other mammals or broods of poikilotherms, but some species of fish and crocodilians have the potential for dominance among broodmates. PMID:16602272

  11. Health impact associated with vertebral deformities: results from the European Vertebral Osteoporosis Study (EVOS).

    PubMed

    Matthis, C; Weber, U; O'Neill, T W; Raspe, H

    1998-01-01

    To study the association between vertebral deformities and subjective health outcome indicators, including back pain and disability, a cross-sectional survey with spinal radiographs and personal interviews was carried out in 36 study centres in 19 European countries on a total of 15,570 men and women aged 50-79 years (population-based stratified random samples). No interventions were done. The main outcome measures were the presence and intensity of current and previous back pain, functional capacity (ADL questionnaire) and overall subjective health. The presence and intensity of back pain and functional and health impairments varied within wide ranges with no obvious regional pattern. However, the associations between negative health outcomes and vertebral deformity were homogeneous between countries and between centres within countries. In logistic regression analyses weak but significant associations between the presence of vertebral deformities and various health indicators were demonstrated. The magnitude of the associations increased with severity and number of deformities. Compared with subjects without deformities those with low-grade deformities had no or only a weakly elevated risk for back pain, disability and impaired subjective health (odds ratios (OR) 1.2-1.3). The odds ratios increased for individuals with single severe deformities (OR 1.3-2.1) and were highest in those with multiple severe deformities (OR 1.7-4.2). The associations between vertebral deformities and negative health outcomes were stronger in men than in women. In this cross-sectional study radiologically assessed vertebral deformities were therefore weakly associated with both current and previous back pain as well as with functional and health impairments in both women and men. Multiple severe deformities were associated with severe and disabling back pain with stronger effects in men. PMID:10024907

  12. Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs

    PubMed Central

    Wong, Siew Fen Lisa; Agarwal, Vikram; Mansfield, Jennifer H.; Denans, Nicolas; Schwartz, Matthew G.; Prosser, Haydn M.; Pourquié, Olivier; Bartel, David P.; Tabin, Clifford J.; McGlinn, Edwina

    2015-01-01

    The Hox genes play a central role in patterning the embryonic anterior-to-posterior axis. An important function of Hox activity in vertebrates is the specification of different vertebral morphologies, with an additional role in axis elongation emerging. The miR-196 family of microRNAs (miRNAs) are predicted to extensively target Hox 3′ UTRs, although the full extent to which miR-196 regulates Hox expression dynamics and influences mammalian development remains to be elucidated. Here we used an extensive allelic series of mouse knockouts to show that the miR-196 family of miRNAs is essential both for properly patterning vertebral identity at different axial levels and for modulating the total number of vertebrae. All three miR-196 paralogs, 196a1, 196a2, and 196b, act redundantly to pattern the midthoracic region, whereas 196a2 and 196b have an additive role in controlling the number of rib-bearing vertebra and positioning of the sacrum. Independent of this, 196a1, 196a2, and 196b act redundantly to constrain total vertebral number. Loss of miR-196 leads to a collective up-regulation of numerous trunk Hox target genes with a concomitant delay in activation of caudal Hox genes, which are proposed to signal the end of axis extension. Additionally, we identified altered molecular signatures associated with the Wnt, Fgf, and Notch/segmentation pathways and demonstrate that miR-196 has the potential to regulate Wnt activity by multiple mechanisms. By feeding into, and thereby integrating, multiple genetic networks controlling vertebral number and identity, miR-196 is a critical player defining axial formulae. PMID:26283362

  13. Dysfunctional Microcirculation of the Lumbar Vertebral Marrow Prior to the Bone Loss and Intervertebral Discal Degeneration

    PubMed Central

    Lu, Guang-ming

    2015-01-01

    Study Design. Descriptive study, stratified sampling. Objective. Using dynamic computed tomographic perfusion (CTP) to explore the age-related distribution patterns of the microcirculation perfusion in the vertebral marrow, the vertebral bone mineral density (BMD), and the intervertebral discal degeneration (IDD) further to discuss the possible causation between them. Summary of Background Data. A latest viewpoint deemed that reduced blood supply of the vertebral marrow was correlated with an increased incidence of IDD and loss of BMD. However, the causative relationship between them needs more investigation. Methods. One hundred eighty-six general people were randomly enrolled by stratified sampling and grouped by age: 15 years or less, 16 to 25 years, 26 to 35 years, 36 to 45 years, 46 to 55 years, 56 to 65 years, 66 to 75 years, and 76 years or more. Both CTP and BMD of the third and fourth lumbar vertebral marrow were measured, and the IDD incidence of the third-fourth vertebrae was assessed. The temporal-spatial distribution patterns of the age-related changes of CTP, BMD, and IDD were described, and the correlations between them were calculated. Results. Microcirculatory perfusion of the vertebral marrow developed to maturate by 25 years, maintained stable at 35 years, and then declined by age after 35 years. BMD grew to a peak phase in 26 to 45 years and then dropped by years. However, IDD presented a sudden increase after 45 years of age. CTP (blood flow [r = 0.806], blood volume [r = 0.685], and permeability [r = 0.619]) showed strong positive correlations and CTP (time to peak [r = −0.211], mean transit time [r = −0.598]) showed negative correlations with BMD. Meanwhile, CTP (blood flow [r = −0.815], blood volume [r = −0.753], and permeability [r = −0.690]) had strong negative correlations and CTP (time to peak [r = 0.323] and mean transit time [r = 0.628]) had positive correlations with the incidence of IDD. Conclusion. Aging-related decrease

  14. Reintroduction of locally extinct vertebrates impacts arid soil fungal communities.

    PubMed

    Clarke, Laurence J; Weyrich, Laura S; Cooper, Alan

    2015-06-01

    Introduced species have contributed to extinction of native vertebrates in many parts of the world. Changes to vertebrate assemblages are also likely to alter microbial communities through coextinction of some taxa and the introduction of others. Many attempts to restore degraded habitats involve removal of exotic vertebrates (livestock and feral animals) and reintroduction of locally extinct species, but the impact of such reintroductions on microbial communities is largely unknown. We used high-throughput DNA sequencing of the fungal internal transcribed spacer I (ITS1) region to examine whether replacing exotic vertebrates with reintroduced native vertebrates led to changes in soil fungal communities at a reserve in arid central Australia. Soil fungal diversity was significantly different between dune and swale (interdune) habitats. Fungal communities also differed significantly between sites with exotic or reintroduced native vertebrates after controlling for the effect of habitat. Several fungal operational taxonomic units (OTUs) found exclusively inside the reserve were present in scats from reintroduced native vertebrates, providing a direct link between the vertebrate assemblage and soil microbial communities. Our results show that changes to vertebrate assemblages through local extinctions and the invasion of exotic species can alter soil fungal communities. If local extinction of one or several species results in the coextinction of microbial taxa, the full complement of ecological interactions may never be restored. PMID:25943906

  15. Correlation between Hox code and vertebral morphology in archosaurs.

    PubMed

    Böhmer, Christine; Rauhut, Oliver W M; Wörheide, Gert

    2015-07-01

    The relationship between developmental genes and phenotypic variation is of central interest in evolutionary biology. An excellent example is the role of Hox genes in the anteroposterior regionalization of the vertebral column in vertebrates. Archosaurs (crocodiles, dinosaurs including birds) are highly variable both in vertebral morphology and number. Nevertheless, functionally equivalent Hox genes are active in the axial skeleton during embryonic development, indicating that the morphological variation across taxa is likely owing to modifications in the pattern of Hox gene expression. By using geometric morphometrics, we demonstrate a correlation between vertebral Hox code and quantifiable vertebral morphology in modern archosaurs, in which the boundaries between morphological subgroups of vertebrae can be linked to anterior Hox gene expression boundaries. Our findings reveal homologous units of cervical vertebrae in modern archosaurs, each with their specific Hox gene pattern, enabling us to trace these homologies in the extinct sauropodomorph dinosaurs, a group with highly variable vertebral counts. Based on the quantifiable vertebral morphology, this allows us to infer the underlying genetic mechanisms in vertebral evolution in fossils, which represents not only an important case study, but will lead to a better understanding of the origin of morphological disparity in recent archosaur vertebral columns. PMID:26085583

  16. Candidal Vertebral Osteomyelitis in the Midst of Renal Disorders.

    PubMed

    Gopinathan, Anusha; Kumar, Anil; Rao, Srivatsa Nagaraja; Kumar, Krishna; Karim, Shamsul

    2016-04-01

    Vertebral osteomyelitis also known as discitis/pyogenic spondylitis refers to inflammation of the vertebral disc space. It is commonly seen in men and adults more than 50 years of age. Fungal osteomyelitis is a rare scenario compared to its bacterial counterpart. Spinal epidural abscess is a dangerous complication associated with vertebral osteomyelitis. Here, we report two cases of vertebral osteomyelitis caused by Candida tropicalis in patients with renal disorders (stage 5 chronic kidney disease and nephropathy). One of the case discussed here presented with spinal epidural abscess. Both the patients were started on antifungal therapy. One patient responded to treatment while the other was lost to follow up. PMID:27190806

  17. Candidal Vertebral Osteomyelitis in the Midst of Renal Disorders

    PubMed Central

    Kumar, Anil; Rao, Srivatsa Nagaraja; Kumar, Krishna; Karim, Shamsul

    2016-01-01

    Vertebral osteomyelitis also known as discitis/pyogenic spondylitis refers to inflammation of the vertebral disc space. It is commonly seen in men and adults more than 50 years of age. Fungal osteomyelitis is a rare scenario compared to its bacterial counterpart. Spinal epidural abscess is a dangerous complication associated with vertebral osteomyelitis. Here, we report two cases of vertebral osteomyelitis caused by Candida tropicalis in patients with renal disorders (stage 5 chronic kidney disease and nephropathy). One of the case discussed here presented with spinal epidural abscess. Both the patients were started on antifungal therapy. One patient responded to treatment while the other was lost to follow up. PMID:27190806

  18. Correlation between Hox code and vertebral morphology in archosaurs

    PubMed Central

    Böhmer, Christine; Rauhut, Oliver W. M.; Wörheide, Gert

    2015-01-01

    The relationship between developmental genes and phenotypic variation is of central interest in evolutionary biology. An excellent example is the role of Hox genes in the anteroposterior regionalization of the vertebral column in vertebrates. Archosaurs (crocodiles, dinosaurs including birds) are highly variable both in vertebral morphology and number. Nevertheless, functionally equivalent Hox genes are active in the axial skeleton during embryonic development, indicating that the morphological variation across taxa is likely owing to modifications in the pattern of Hox gene expression. By using geometric morphometrics, we demonstrate a correlation between vertebral Hox code and quantifiable vertebral morphology in modern archosaurs, in which the boundaries between morphological subgroups of vertebrae can be linked to anterior Hox gene expression boundaries. Our findings reveal homologous units of cervical vertebrae in modern archosaurs, each with their specific Hox gene pattern, enabling us to trace these homologies in the extinct sauropodomorph dinosaurs, a group with highly variable vertebral counts. Based on the quantifiable vertebral morphology, this allows us to infer the underlying genetic mechanisms in vertebral evolution in fossils, which represents not only an important case study, but will lead to a better understanding of the origin of morphological disparity in recent archosaur vertebral columns. PMID:26085583

  19. Enamel-like apatite crown covering amorphous mineral in a crayfish mandible.

    PubMed

    Bentov, Shmuel; Zaslansky, Paul; Al-Sawalmih, Ali; Masic, Admir; Fratzl, Peter; Sagi, Amir; Berman, Amir; Aichmayer, Barbara

    2012-01-01

    Carbonated hydroxyapatite is the mineral found in vertebrate bones and teeth, whereas invertebrates utilize calcium carbonate in their mineralized organs. In particular, stable amorphous calcium carbonate is found in many crustaceans. Here we report on an unusual, crystalline enamel-like apatite layer found in the mandibles of the arthropod Cherax quadricarinatus (freshwater crayfish). Despite their very different thermodynamic stabilities, amorphous calcium carbonate, amorphous calcium phosphate, calcite and fluorapatite coexist in well-defined functional layers in close proximity within the mandible. The softer amorphous minerals are found primarily in the bulk of the mandible whereas apatite, the harder and less soluble mineral, forms a wear-resistant, enamel-like coating of the molar tooth. Our findings suggest a unique case of convergent evolution, where similar functional challenges of mastication led to independent developments of structurally and mechanically similar, apatite-based layers in the teeth of genetically remote phyla: vertebrates and crustaceans. PMID:22588301

  20. Enamel-like apatite crown covering amorphous mineral in a crayfish mandible

    PubMed Central

    Bentov, Shmuel; Zaslansky, Paul; Al-Sawalmih, Ali; Masic, Admir; Fratzl, Peter; Sagi, Amir; Berman, Amir; Aichmayer, Barbara

    2012-01-01

    Carbonated hydroxyapatite is the mineral found in vertebrate bones and teeth, whereas invertebrates utilize calcium carbonate in their mineralized organs. In particular, stable amorphous calcium carbonate is found in many crustaceans. Here we report on an unusual, crystalline enamel-like apatite layer found in the mandibles of the arthropod Cherax quadricarinatus (freshwater crayfish). Despite their very different thermodynamic stabilities, amorphous calcium carbonate, amorphous calcium phosphate, calcite and fluorapatite coexist in well-defined functional layers in close proximity within the mandible. The softer amorphous minerals are found primarily in the bulk of the mandible whereas apatite, the harder and less soluble mineral, forms a wear-resistant, enamel-like coating of the molar tooth. Our findings suggest a unique case of convergent evolution, where similar functional challenges of mastication led to independent developments of structurally and mechanically similar, apatite-based layers in the teeth of genetically remote phyla: vertebrates and crustaceans. PMID:22588301