Wnt-signal transduction through ?-catenin is thought to require the inhibition of GSK3 by Frat/GBP. To investigate the role of Frat in mammalian development, we have generated mice with targeted mutations in all three murine Frat homologs. We show that Frat is normally expressed at sites of active Wnt signaling. Surprisingly, ...

WNT/planar cell polarity (PCP) signaling pathway controls tissue polarity and cell movement through the activation of RHOA, c-Jun N-terminal kinase (JNK), and nemo-like kinase (NLK) signaling cascades. PCP is induced in Drosophila by the asymmetrical localization of Frizzled-Dishevelled-Diego-Starry night (Flamingo) complex and Van ...

The effects of Wnt7b on lung development were examined using a conditional Wnt7b-null mouse. Wnt7b-null lungs are markedly hypoplastic, yet display largely normal patterning and cell differentiation. In contrast to findings in prior hypomorphic Wnt7b models, we find decreased replication of both developing ...

The Wnt genes encode a large family of secreted glycoproteins that play important roles in controlling tissue patterning, cell fate and proliferation during development. Currently, little is known regarding the role(s) of Wnt genes during prostate gland development. The present study examines the role of the noncanonical Wnt5a during ...

PURPOSE OF REVIEW: The Wnt/?-catenin signaling pathway plays a critical role in development and adult tissue homeostasis. Recent investigations implicate Wnt/?-catenin signaling in abnormal wound repair and fibrogenesis. The purpose of this review is to highlight recent key studies that support ...

Wnt proteins play major roles in development and differentiation, and abnormalities in their regulation are believed to contribute to the formation of many cancers, including colorectal malignancies. As a result, there has been an interest in identifying small molecule inhibitors of Wnt signaling as tool compounds ...

WNT GENES ENCODE A LARGE FAMILY OF SECRETED SIGNALING MOLECULES ESSENTIAL FOR DEVELOPMENT AND ONCOGENESIS. WNT-1, THE FOUNDING MEMBER OF THE WNT GENE FAMILY, WAS INITIALLY IDENTIFIED AS AN ONCOGENE. Ectopic wnt-1 expression causes mammary tumorigenesis in...

WNT GENES ENCODE A LARGE FAMILY OF SECRETED SIGNALING MOLECULES ESSENTIAL FOR DEVELOPMENT AND ONCOGENESIS. WNT-1, THE FOUNDING MEMBER OF THE WNT GENE FAMILY, WAS INITIALLY IDENTIFIED AS AN ONCOGENE. Ectopic wnt-1 expression causes mammary tumorigenesis in...

Purpose:The Wnt/?-catenin (?-cat) signaling cascade is a key regulator of development, and dysregulation of Wnt/?-cat contributes to selected cancers, such as colorectal, breast and hepatocellular carcinoma, through abnormal activation of Wnt target genes. To identify novel modulators of the ...

AbstractMesodermal tissue with heart forming potential (cardiogenic mesoderm) is induced during gastrulation. This cardiogenic mesoderm later differentiates into heart muscle tissue (myocardium) and non-muscular heart tissue. Inhibition of Wnt/?-catenin signaling is known to be required early for induction of cardiogenic mesoderm; however, the identity of ...

In a collaborative study, we investigated four 46,XX adolescent girls with Mayer-Rokitansky-K�ster-Hauser syndrome and hyperandrogenism. Molecular analysis of the WNT4 gene permitted us to identify a new mutation (p.A233T). Functional studies revealed partial repression of steroidogenic enzymes (normal repression of HSD3B2) contrasting with the abnormal ...

The Wnt family of secreted signaling molecules has profound effects on diverse developmental processes, including the fate of mesenchymal progenitors. While activation of Wnt signaling blocks adipogenesis, inhibition of endogenous Wnt/beta-catenin signaling by ...

... I have shown that Wnt5a, which functions in non-canonical Wnt signaling, promoted proliferation, cell survival and network formation on endothelial ...

... Children's Hospital ... wnt genes encode a large family of secreted signaling molecules essential for development and oncogenesis. ...

... Title : Deregulated Wnt Signaling in Prostate Cancer. ... Corporate Author : FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA. ...

In the embryonic neural tube, multiple signaling pathways work in concert to create functional neuronal circuits in the adult spinal cord. In the ventral neural tube, Sonic hedgehog (Shh) acts as a graded morphogen to specify neurons necessary for movement. In the dorsal neural tube, bone morphogenetic protein (BMP) and Wnt signals ...

Monoaminergic neurons (serotonergic (5HT) and dopaminergic (mdDA)) in the brainstem project axons along the anterior-posterior axis. Despite their important physiological functions and implication in disease, the molecular mechanisms that dictate the formation of these projections along the anterior-posterior axis remain unknown. Here we reveal a novel requirement for ...

Bone morphogenetic protein 4 (Bmp4) is essential for lung development. To define the intracellular signaling mechanisms by which Bmp4 regulates lung development, BMP-specific Smad1 or Smad5 was selectively knocked out in fetal mouse lung epithelial cells. Abrogation of lung epithelial-specific Smad1, but not Smad5, resulted in retardation of lung branching morphogenesis and ...

Wnt signaling is a crucial component of the cell machinery orchestrating a series of physiological processes such as cell survival, proliferation, and migration. Among the plethora of roles that Wnt signaling plays, its canonical branch regulates eye organogenesis and angiogenesis. Mutations in the genes encoding ...

ICAT (Inhibitor of ?-catenin and T cell factor) inhibits the interaction between ?-catenin and TCF/LEF transcription factor and serves as a negative regulator of Wnt signaling. In a subset of ICAT knockout mice, significant delay in the ureteric bud branching and renal agenesis are observed. In order to examine the process of this developmental defect, ...

Autosomal recessive primary microcephaly (MCPH) is a neural developmental disorder in which patients display significantly reduced brain size. Mutations in Abnormal Spindle Microcephaly (ASPM) are the most common cause of MCPH. Here, we investigate the underlying functions of Aspm in brain development and find that Aspm expression is critical for proper neurogenesis and ...

Robinow syndrome is a skeletal dysplasia with both autosomal dominant and autosomal recessive inheritance patterns. It is characterized by short stature, limb shortening, genital hypoplasia, and craniofacial abnormalities. The etiology of dominant Robinow syndrome is unknown; however, the phenotypically more severe autosomal recessive form of Robinow syndrome has been ...

... Supporting this epistasis, LRP6 induction of of LRP6 can bind Wnt-1 and form a complex with Fz in a Wnt- Xnr3/sia was antagonized by Axin24, by ...

... was engineered to over express the Wnt3 gene. ... 20% more expression compared to control (Figure 1B). ... Wnt3-IRES-Luc mice compared to controls. ...

The interplay between canonical and non-canonical Wnt pathways in development and tumorigenesis is tightly regulated. In this review we will describe the yin and the yang of canonical and non-canonical Wnt signaling pathways during melanocyte development, and melanoma genesis. Canonical Wnt ...

Wnt genes encode a large family of secreted signaling molecules related to the Drosophila pattern regulating gene wingless. Several members of the Wnt family have been implicated in mammary tumorigenesis suggesting that Wnt-activated pathways are a normal...

Wnt genes encode a large family of secreted signaling molecules related to the Drosophila pattern regulating gene wingless. Several members of the Wnt family are implicated in mammary tumorigenesis suggesting that Wnt-activated pathways are a normal compo...

Wnt genes encode a large family of secreted signaling molecules related to the Drosophila pattern regulating gene wingless. Several members of the Wnt family are implicated in mammary tumorigenesis suggesting that Wnt-activated pathways are a normal compo...

Morphogenesis during eye development requires retinoic acid (RA) receptors plus RA-synthesizing enzymes, and loss of RA signaling leads to ocular disorders associated with loss of Pitx2 expression in perioptic mesenchyme. Several Wnt signaling components are expressed in ocular tissues during eye development including Dkk2, encoding an ...

Activation of the Wnt signaling pathway via mutation of the adenomatous polyposis coli gene (APC) is a critical event in the development of colon cancer. For colon carcinogenesis, however, constitutive signaling through the canonical Wnt pathway is not a singular event. Here we review how canonical ...

DiGeorge syndrome (DGS) is a common genetic disease characterized by pharyngeal apparatus malformations and defects in cardiovascular, craniofacial and glandular development. TBX1 is the most likely candidate disease-causing gene and is located within a 22q11.2 chromosomal deletion that is associated with most cases of DGS. Here, we show that canonical Wnt�?-catenin ...

The non-canonical Wnt/Ca(2+) signaling cascade is less characterized than their canonical counterpart, the Wnt/?-catenin pathway. The non-canonical Wnt signaling pathways are diverse, defined as planer cell polarity pathway, Wnt-RAP1 signaling pathway, ...

Mullerian inhibiting substance type II receptor (MISRII) is a member of the transforming growth factor-beta superfamily. Mutations in mullerian inhibiting substance (MIS) or MISRII cause male sexual abnormalities, persistent mullerian duct syndrome, and pseudohermaphroditism. The spatial and temporal regulation of MIS and MISRII is important for its biological action. Male ...

The work done in this grant aims at elucidating the function of the Wnt signaling molecules in cancer. Wnt proteins are secreted and play important roles in the control over growth, in particular in the mammary gland. Wnt genes can also can act as oncogen...

Over expression of Wnt proteins has long been know to lead to mammary hyperplasia and neoplasia in the mouse mammary gland. Unregulated Wnt signaling may also contribute to the formation of human breast tumours as over expression of Wnt proteins and nucle...

Mutations in bone morphogenetic protein (BMP) receptor II (BMPRII) are associated with pulmonary artery endothelial cell (PAEC) apoptosis and the loss of small vessels seen in idiopathic pulmonary arterial hypertension. Given the low penetrance of BMPRII mutations, abnormalities in other converging signaling pathways may be necessary for disease ...

Wnt signalling pathways have been shown to play key roles in both normal development and tumorigenesis. Progression of many human cancers is associated with defined mutations in Wnt pathway components that result in dysregulated ?-catenin-mediated gene transcription. Although Wnt pathway mutations are rare in ...

Abnormal fibrillinogenesis is associated with connective tissue disorders (CTDs), including Marfan syndrome (MFS), systemic sclerosis (SSc) and Tight-skin (Tsk) mice. We have previously shown that TGF-? and Wnt stimulate fibrillin-1 assembly and that fibrillin-1 and the developmental regulator CCN3 are both highly increased in Tsk skin. We investigated the ...

Wnt signaling in the thymus is regulated by differential expression of intracellular signaling in the thymus, but the stages in which it occurs and the molecular mechanisms underlying Wnt responsiveness have development -catenin Dickkopf Thymocyte differentiation in the thymus involves a series of discrete ...

The Wnt family of secreted signaling molecules plays crucial roles in mammary tumorigenesis and embryonic development. The frizzled family of serpentine receptors has been shown to be capable of transducing the Wnt signal suggesting that a frizzled protei...

Evolutionarily conserved gene clusters are interesting for two reasons: (1) they may illuminate ancient events in genome evolution and (2) they may reveal ongoing stabilizing selection; that is, the conservation of gene clusters may have functional significance. To test if the Wnt family of signaling factors exhibits conserved clustering in basal metazoans ...

Wnt signaling controls a variety of developmental and homeostatic events. As a key component of Wnt signaling, Dishevelled (Dvl/Dsh) protein relays Wnt signals from receptors to downstream effectors. In the canonical Wnt pathway that depends on the ...

... Title : Role of the Mouse Pygopus 2 Gene and Wnt Signaling in Normal and Malignant Development of Mammary Glands and Hair Follicles. ...

... test the hypothesis that activated canonical Wnt signaling identifies mammary stem cells and mammary tumor cells with cancer stem cell properties. ...

... Title : Canonical Wnt Signaling as a Specific Marker of Normal and Tumorigenic Mammary Stem Cells. Descriptive Note : Annual rept. ...

... Title : Canonical Wnt Signaling as a Specific Mark of Normal and Tumorigenic Mammary Stem Cells. Descriptive Note : Annual rept. ...

Bicaudal C homologue 1 (Bicc1) knock-out in mice causes polycystic kidney disease and pancreas development defects, including a reduction in insulin-producing ?-cells and ensuing diabetes. We therefore screened 137 patients with renal abnormalities or association of early-onset diabetes and renal disease for genetic alterations in BICC1. We identified two heterozygous ...

Glycogen synthase kinase 3 (GSK3) is an essential component of the Wnt signaling pathway and plays important roles in regulating cell proliferation, differentiation, and apoptosis. As GSK3 is abnormally upregulated in several diseases including type II diabetes, Alzheimer�s disease and cancer, it has been regarded as a potential drug ...

Wnt signal transduction plays a crucial role in stem cell proliferation and regeneration. When canonical Wnt signaling is low, heads develop, and when it is high, tails are formed. In planarians, Wnt transcription is activated by wounding in a beta-catenin-independent way. Hedgehog is one of ...

Wnt signal transduction plays a crucial role in stem cell proliferation and regeneration. When canonical Wnt signaling is low, heads develop, and when it is high, tails are formed. In planarians, Wnt transcription is activated by wounding in a ?-catenin�independent way. Hedgehog is one of the ...

Dysregulated Wnt signaling is the cause of many human tumors, and induces breast cancer in mice. We have previously found that the initiating response to Wnt signaling is the accumulation of breast somatic stem cells. We propose that tumor development is ...

Several of the Wnt genes family are expressed and differentially regulated during breast development. The Wnt signal transduction pathway has been implicated in mammary tumorigenesis in different species as well as in human breast cancer cell lines. The v...

The Drosophila porcupine gene is required for secretion of wingless and other Wnt proteins, and sporadic mutations in its unique human ortholog, PORCN, cause a pleiotropic X-linked dominant disorder, focal dermal hypoplasia (FDH, also known as Goltz syndrome). We generated a conditional allele of the X-linked mouse Porcn gene and analyzed its requirement in ...

Wnt signaling regulates a wealth of aspects of nervous system development and function in embryonic stages and in adulthood. The expression of Wnt ligands and components of the Wnt signaling machinery in early stages of neural development has been related to its role in neurite patterning and ...

Wnt signaling plays an essential role in the development of mammalian central nervous system. We investigated the impact of activation/inhibition of the Wnt signaling pathway on neuronal/glial differentiation in neurospheres derived from neonatal mouse forebrains. For short term alterations, neurospheres were ...

Wnt signalling is an evolutionarily conserved pathway that directs cell-fate determination and morphogenesis during metazoan development. Wnt ligands are secreted glycoproteins that act at a distance causing a wide range of cellular responses from stem cell maintenance to cell death and cell proliferation. How Wnt ...

in the regulation of sodium homeostasis via SGK1. MAIN TEXT Introduction The Wnt signaling system consists in the regulation of sodium transport and volume homeostasis (3). Wnt signaling The denomination Wnt is derived from. The family of Wnt's consists of 7 members in ...

Wnt proteins comprise a large class of secreted signaling molecules with key roles during embryonic development and throughout adult life. Recently, much effort has been focused on understanding the factors that regulate Wnt signal production. For example, Porcupine and Wntless/Evi/Sprinter have been identified as ...

Lrp6 is generally described as a receptor required for signal transduction in the Wnt/beta-catenin pathway. Wnt5a, however, is a Wnt ligand that usually does not activate Wnt/beta-catenin but rather activates noncanonical Wnt signaling. We have ...

Knowledge of the molecular mechanisms regulating cell ingression, epithelial-mesenchymal transition and migration movements during amniote gastrulation is steadily improving. In the frog and fish embryo, Wnt5 and Wnt11 ligands are expressed around the blastopore and play an important role in regulating cell movements associated with gastrulation. In the ...

The canonical Wnt/?-catenin pathway plays crucial roles in various aspects of lung morphogenesis and regeneration/repair. Here, we examined the lung phenotype and function in mice lacking the Wnt/?-catenin antagonist Chibby (Cby). In support of its inhibitory role in canonical Wnt signaling, expression of ?-catenin ...

Diabetic kidney disease (DKD) is the single most common cause of albuminuria and end-stage kidney disease in the United States. We found increased expression of Wnt/?-catenin (Ctnnb1) pathway transcripts and proteins in glomeruli and podocytes of patients and mouse models of DKD. Mice with podocyte-specific expression of stabilized Ctnnb1 exhibited basement membrane ...

The canonical Wnt/?-catenin pathway plays crucial roles in various aspects of lung morphogenesis and regeneration/repair. Here, we examined the lung phenotype and function in mice lacking the Wnt/?-catenin antagonist Chibby (Cby). In support of its inhibitory role in canonical Wnt signaling, expression of ?-catenin ...

... systematically analyzed these mice at various ages at the anatomical and histological level for abnormalities in prostate development and histology ...

Vertebrate dorsoventral patterning requires both Wnt8 and BMP signaling. Because of their multiple interactions, discerning roles attributable specifically to Wnt8 independent of BMP has been a challenge. For example, Wnt8 represses the dorsal organizer that negatively regulates ventral BMP ...

Mesenchymal cells underlying the definitive endoderm in vertebrate animals play a vital role in digestive and respiratory organogenesis. Although several signaling pathways are implicated in foregut patterning and morphogenesis, and despite the clinical importance of congenital tracheal and esophageal malformations in humans, understanding of molecular mechanisms that allow a ...

Tissue-specific stem cells combine proliferative and asymmetric divisions to balance self-renewal with differentiation. Tight regulation of the orientation and plane of cell division is crucial in this process. Here, we study the reproducible pattern of anterior-posterior-oriented stem cell-like divisions in the Caenorhabditis elegans seam epithelium. In a genetic screen, we identified an alg-1 ...

... the initiation, progression and metastasis of spontaneous autochthonous prostate cancer and the emergence of the castration resistant phenotype. ...

Wnt signaling is known to be required for the normal development of the vertebrate midbrain and hindbrain, but genetic loss of function analyses in the mouse and zebrafish yield differing results regarding the relative importance of specific Wnt loci. In the zebrafish, Wnt1 and Wnt10b ...

BackgroundKlotho was originally characterized as an anti-aging gene that predisposed Klotho-deficient mice to a premature aging-like syndrome. Recently, KLOTHO was reported to function as a secreted Wnt antagonist and as a tumor suppressor. Epigenetic gene silencing of secreted Wnt antagonists is considered a common event in a wide range of human ...

Wnt/Wg genes play a critical role in the development of various organisms. For example, the Wnt/beta-catenin signal promotes heart formation and cardiomyocyte differentiation in mice. Previous studies have shown that RGS19 (regulator of G protein signaling 19), which has Galpha subunits with GTPase activity, ...

Wnt/Wg genes play a critical role in the development of various organisms. For example, the Wnt/?-catenin signal promotes heart formation and cardiomyocyte differentiation in mice. Previous studies have shown that RGS19 (regulator of G protein signaling 19), which has G? subunits with GTPase activity, inhibits the ...

WNT signaling is a fundamental molecular pathway in both embryogenesis and disease. Nephron development is dependent on WNT signaling. The nephron epithelia proximal to the collecting duct develop from progenitor cells in the metanephric mesenchyme. The process involves formation of proto-epithelial cell ...

BackgroundWnt signaling affects fundamental development pathways by regulating cell proliferation and differentiation. Aberrant activation of Wnt/?-catenin signaling promotes the development of several cancers and is an attractive target for chemopreventive and chemotherapeutic agents.ResultsIn order to identify ...

... Increased expression of Wnt5a has been reported in malignant melanoma, primary human breast cancer, and colon cancer, ...

Truncating GLI3 mutations in Pallister-Hall Syndrome with renal malformation suggests a requirement for Hedgehog signaling during renal development. HH-dependent signaling increases levels of GLI transcriptional activators and decreases processing of GLI3 to a shorter transcriptional repressor. Previously, we showed that Shh-deficiency interrupts early ...

Truncating GLI3 mutations in Pallister-Hall Syndrome with renal malformation suggests a requirement for Hedgehog signaling during renal development. HH-dependent signaling increases levels of GLI transcriptional activators and decreases processing of GLI3 to a shorter transcriptional repressor. Previously, we showed that Shh-deficiency interrupts early ...

The Wnt signaling pathway is one of the central morphogenic signaling pathways regulating early vertebrate development. In recent years it�s become clear that the Wnt pathway also regulates many aspects of nervous system development from the patterning stage through the regulation of neural plasticity. In this ...

?-catenin-dependent Wnt signaling is initiated as Wnt binds to both the receptor FZD and coreceptor LRP5/6, which then assembles a multimeric complex at the cytoplasmic membrane face to recruit and inactivate the kinase GSK3. The large number and sequence diversity of Wnt isoforms suggest the possibility of ...

We have previously demonstrated that Gpr177, the mouse orthologue of Drosophila Wls/Evi/Srt, is required for establishment of the anterior-posterior axis. The Gpr177 null phenotype is highly reminiscent to the loss of Wnt3, the earliest abnormality among all Wnt knockouts in mice. The expression of Gpr177 in various cell types and ...

Wnt5a is a member of the Wingless-related/MMTV-integration family of secreted growth factors, which are involved in a wide range of cellular processes. Wnt signaling can be broadly divided into two categories the canonical, �-catenin-dependent pathway and the non-canonical �-catenin-independent pathway. Wnt5a ...

The work done in this grant was aimed at elucidating the function of the Wnt signaling molecules in cancer, in particular at isolating a receptor. Wnt proteins are secreted and play important growth controlling roles, in particular in the mammary gland. T...

The work done in this grant aims at elucidating the function of the Wnt signaling molecules in cancer. Wnt proteins are secreted and play important growth controlling roles, in particular in the mammary gland. They can act as oncogenes in mouse mammary tu...

Convergent extension (CE) cell movements during gastrulation mediate extension of the anterior-posterior body axis of vertebrate embryos. Non-canonical Wnt5 and Wnt11 signalling is essential for normal CE movements in vertebrate gastrulation. Here, we show that morpholino (MO)-mediated double knock-down of the Fyn and Yes tyrosine ...

Lrp5/6 are crucial coreceptors for Wnt/?-catenin signaling, a pathway biochemically distinct from noncanonical Wnt signaling pathways. Here, we examined the possible participation of Lrp5/6 in noncanonical Wnt signaling. We found that Lrp6 physically interacts with ...

Wnt signaling is known to regulate multiple processes including angiogenesis, inflammation, and fibrosis. Here, we identified a novel inhibitor of the Wnt pathway, pigment epithelium-derived factor (PEDF), a multifunctional serine proteinase inhibitor. Both overexpression of PEDF in transgenic mice and administration of PEDF protein ...

The Wnt/?-catenin signaling pathway plays essential roles during development and adult tissue homeostasis. Inappropriate activation of the pathway can result in a variety of malignancies. Protein kinases have emerged as key regulators at multiple steps of the Wnt pathway. In this review, we present a synthesis covering the latest ...

It turns out that Wnt signaling controls this process of self-renewal, operating as a kind of master switch between proliferation of stem cells and differentiation into epithelial cells. Several studies have shown that Wnt-target gene expression occurs in a gradient that is strongest at the base of the intestinal crypt and weakens ...

... Descriptors : *SIGNALS, *MAMMARY GLANDS, *GROWTH(PHYSIOLOGY), *PROGESTERONE, *BREAST CANCER, MOLECULES, NEOPLASMS ...

... of the mammary gland, and the pathways that lead to tumor formation. Descriptors : *NEOPLASMS, *SIGNALS, *MAMMARY GLANDS, *GROWTH ...

SUMMARYWnt/?-catenin and NF-?B signaling mechanisms provide central controls in development and disease, but how these pathways intersect is unclear. Using hair follicle induction as a model system, we show that patterning of dermal Wnt/?-catenin signaling requires epithelial ?-catenin activity. We find that ...

BackgroundBrisken et al (2000) showed that Wnt4 null mammary glands were deficient in early lobuloalveolar mammary outgrowth during pregnancy, and implicated Wnt4 as an effector for the progesterone-induced mammary growth program. Though ectopic Wnt1 signaling is known to be mitogenic and oncogenic, no endogenously ...

Ror1 is a member of the Ror-family receptor tyrosine kinases. Ror1 is broadly expressed in various tissues and organs during mouse embryonic development. However, so far little is known about its function. The closely related family member Ror2 was shown to play a crucial role in skeletogenesis and has been shown to act as a co-receptor for Wnt5a mediating non-canonical ...

The highly regulated Wnt signaling cascade plays a decisive role during embryonic patterning and cell-fate determination. The inappropriate expression of Wnt target genes, resulting from deregulation of this pathway, is also implicated in tumorigenesis. Thus, regulation of this pathway is of paramount importance. The ...

The Wnt pathway effector gene TCF7L2 has been linked to type II diabetes, making it important to study the role of Wnt signaling in diabetes pathogenesis. We examined the expression of multiple Wnt pathway components in pancreases from normal individuals and type II diabetic individuals. Multiple members of the ...

Although it is well known that Wnt and protein kinase C (PKC) signaling pathways are both involved in carcinogenesis and tumor progression, their synergistic contribution to these processes or the crosstalk between them has just recently been approached. The Wnt and PKC signaling are involved in many cellular ...

During metazoan development, Wnt molecules are secreted from Wnt-producing cells, diffuse to target cells, and determine cell fates; therefore, Wnt secretion is tightly regulated. However, the molecular mechanisms controlling Wnt diffusion are not fully elucidated. The specific chondroitin sulfate (CS) structure ...

Glypicans are heparan sulfate proteoglycans that are attached to the cell surface by a GPI (glycosylphosphatidylinositol)anchor. Glypicans regulate the activity of Wnts, Hedgehogs,bone morphogenetic proteins and fibroblast growth factors. In the particular case of Wnts, it has been proposed that GPI-anchored glypicans stimulate Wnt signalling by ...

The Wnt signaling pathway must be properly modulated to ensure an appropriate output: pathological conditions result from either insufficient or excessive levels of Wnt signal. For example, hyperactivation of the Wnt pathway is associated with various cancers and subnormal ...

The Wnt signaling pathway must be properly modulated to ensure an appropriate output: pathological conditions result from either insufficient or excessive levels of Wnt signal. For example, hyperactivation of the Wnt pathway is associated with various cancers and subnormal ...

Disregulated Wnt/beta-catenin signaling has been linked to various human diseases, including cancers. Inhibitors of oncogenic Wnt signaling are likely to have a therapeutic effect in cancers. LRP5 and LRP6 are closely related membrane coreceptors for Wnt proteins. Using a phage-display library, ...

Disregulated Wnt/?-catenin signaling has been linked to various human diseases, including cancers. Inhibitors of oncogenic Wnt signaling are likely to have a therapeutic effect in cancers. LRP5 and LRP6 are closely related membrane coreceptors for Wnt proteins. Using a phage-display library, we ...

Specification and early patterning of the vertebrate heart are dependent on both canonical and noncanonical wingless (Wnt) signal pathways. However, the impact of each Wnt pathway on the later stages of myocardial development and differentiation remains controversial. Here, we report that the components of each Wnt ...

The aberrant activation of the wingless (Wnt) signaling pathway is a key element involved in carcinogenesis as Wnt regulates a variety of cellular processes including proliferation, differentiation, survival, apoptosis and cell motility. Upon Wnt receptor activation, the canonical ...

Signaling by the Wnt family of secreted glycolipoproteins via the transcriptional coactivator beta-catenin controls embryonic development and adult homeostasis. Here we review recent progress in this so-called canonical Wnt signaling pathway. We discuss Wnt ligands, agonists, and antagonists, ...

Signaling by the Wnt family of secreted glycolipoproteins via the transcription co-activator ?-catenin controls embryonic development and adult homeostasis. Here we review recent progresses in this so-called canonical Wnt signaling pathway. We discuss Wnt ligands, agonists and antagonists and ...

. HIGH-RANKED GENE COMBINATIONS RELATED TO CANCER. THE GENES ON THE PTEN DEPENDENT PATHWAY AND WNT fate and deregulation of these pathways demonstrates car- cinogenesis. The PTEN/Akt pathway and Wnt on PTEN/Akt pathway and Wnt signaling pathway. The Wnt signaling pathway ...

Wnt-3a is a representative ligand that activates the beta-catenin-dependent pathway in Wnt signaling and is modified with glycans and palmitate. In this study, we analyzed the relationship between glycosylation and lipidation of Wnt-3a. Secretion of a Wnt-3a mutant that lacks glycosylation ...

Wnt-5a is a representative ligand that activates a ?-catenin-independent pathway in Wnt signalling. In the present paper, the roles of the post-translational modifications in the actions of Wnt-5a were investigated. We found that Wnt-5a is modified with palmitate at ...

DCDC2 is one of the candidate susceptibility genes for dyslexia. It belongs to the superfamily of doublecortin domain containing proteins that bind to microtubules, and it has been shown to be involved in neuronal migration. We show that the Dcdc2 protein localizes to the primary cilium in primary rat hippocampal neurons and that it can be found within close proximity to the ciliary kinesin-2 ...

The association between the wnt signaling pathway and apoptosis has become more firmly established in the recent scientific literature. Many reports indicate that the wnt signaling pathway regulates apoptosis through a variety of mechanisms.The activity of wnt signaling ...

R-spondins are secreted Wnt signalling agonists, which regulate embryonic patterning and stem cell proliferation, but whose mechanism of action is poorly understood. Here we show that R-spondins bind to the orphan G-protein-coupled receptors LGR4 and LGR5 by their Furin domains. Gain- and loss-of-function experiments in mammalian cells and Xenopus embryos ...

DiGeorge syndrome (DGS) is a common genetic disease characterized by pharyngeal apparatus malformations and defects in cardiovascular, craniofacial and glandular development. TBX1 is the most likely candidate disease-causing gene and is located within a 22q11.2 chromosomal deletion that is associated with most cases of DGS. Here, we show that canonical Wnt-beta-catenin ...

The pathology associated with tuberous sclerosis complex (TSC) shows diverse phenotypes that suggest abnormal signaling of multiple pathways. Besides the negative regulatory role of the TSC1/TSC2 proteins on mTOR, we have reported an effect on ?-catenin signaling at the level of the degradation complex in vitro. The TSC1/TSC2 complex ...

Cortical intermediate progenitors (IPs) comprise a secondary neuronal progenitor pool that arises from radial glia (RG). IPs are essential for generating the correct number of cortical neurons, however, the factors that regulate the expansion and differentiation of IPs in the embryonic cortex are largely unknown. In this study, we show that the Wnt-?-catenin pathway (canonical ...

The ATP-dependent chromatin-remodeling enzyme brahma-related gene 1 (BRG1) regulates transcription of specific target genes during embryonic and postnatal development. Deletion of Brg1 from embryonic blood vessels results in yolk sac vascular remodeling defects. We now report that misregulation of the canonical Wnt signaling pathway underlies many Brg1 ...

Osteosarcoma is the most common primary bone malignancy, with a high propensity for local invasion, early metastasis and relapse. While the molecular mechanisms behind osteosarcoma development and metastasis have not yet been fully elucidated, research has highlighted an important role for Wnt signaling. Several Wnt ligands, receptors ...

The WNT signaling pathway plays important roles in the self-renewal and differentiation of mesenchymal stem cells (MSCs). Little is known about WNT signaling in adipocyte differentiation of human MSCs. In this study, we tested the hypothesis that canonical and non-canonical WNTs differentially regulate in vitro ...

Certain WNT and WNT network target genes are expressed at higher or lower levels in chronic lymphocytic leukemia compared with normal B-cells. This includes upregulation of nuclear complex genes, as well as genes for cytoplasmic proteins and WNT ligands and their cognate receptors. In addition, epigenetic silencing of several negative ...

Invasion of human trophoblasts is promoted through activation of wingless (Wnt) signaling, suggesting a role of the pathway in placental development and morphogenesis. However, details on the process such as involvement of canonical and/or noncanonical Wnt signaling cascades as well as their target genes are ...

Misregulation of the Wnt pathway is a common route to cancer, including primary breast cancers. In this issue of Genes & Development, Miranda-Carboni and colleagues (3121�3134) demonstrate that the cyclin-dependent kinase inhibitor p27^Kip1 is ubiquitylated for proteasomal degradation in Wnt10b-induced mammary tumors exclusively ...

Craniosynostosis, a developmental disorder resulting from premature closure of the gaps (sutures) between skull bones, can be caused by excessive intramembranous ossification, a type of bone formation that does not involve formation of a cartilage template (chondrogenesis). Here, we show that endochondral ossification, a type of bone formation that proceeds through a cartilage intermediate, caused ...

Wnt proteins bind to seven-transmembrane Frizzled receptors to mediate the important developmental, morphogenetic, and tissue-regenerative effects of Wnt signaling. Dysregulated Wnt signaling is associated with many cancers. Currently there exist no drug candidates, or even tool compounds that ...

BACKGROUND: Wnt signaling plays critical roles in mammalian lung development. However, Wnt signaling in the development of the zebrafish swimbladder, which is considered as a counterpart of mammalian lungs, have not been explored. To investigate the potential conservation of signaling events in ...

BackgroundWnt signaling plays critical roles in mammalian lung development. However, Wnt signaling in the development of the zebrafish swimbladder, which is considered as a counterpart of mammalian lungs, have not been explored. To investigate the potential conservation of signaling events in ...

Recent studies utilizing small molecule antagonists have revealed that the poly(ADP-ribose) polymerases (PARPs) Tankyrase 1 and 2 are critical regulators of canonical Wnt signaling in some cellular contexts. However, the absence of any activity during zebrafish embryogenesis suggested that the tankyrases may not be general/core components of the ...