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1.
Ectodermal Wnt function as a neural crest inducer   总被引:1,自引:0,他引:1  
Neural crest cells, which generate peripheral nervous system and facial skeleton, arise at the neural plate/ectodermal border via an inductive interaction between these tissues. Wnts and bone morphogenetic proteins (BMPs) play roles in neural crest induction in amphibians and zebrafish. Here, we show that, in avians, Wnt6 is localized in ectoderm and in vivo inhibition of Wnt signaling perturbs neural crest formation. Furthermore, Wnts induce neural crest from naive neural plates in vitro in a defined medium without added factors, whereas BMPs require additives. Our data suggest that Wnt molecules are necessary and sufficient to induce neural crest cells in avian embryos.  相似文献   

2.
Genes associated with Hirschsprung disease, a failure to form enteric ganglia in the hindgut, were highly up-regulated in gut neural crest stem cells relative to whole-fetus RNA. One of these genes, the glial cell line-derived neurotrophic factor (GDNF) receptor Ret, was necessary for neural crest stem cell migration in the gut. GDNF promoted the migration of neural crest stem cells in culture but did not affect their survival or proliferation. Gene expression profiling, combined with reverse genetics and analyses of stem cell function, suggests that Hirschsprung disease is caused by defects in neural crest stem cell function.  相似文献   

3.
Cell line segregation during peripheral nervous system ontogeny   总被引:15,自引:0,他引:15  
The peripheral nervous system of vertebrates arises from the neural crest and the ectodermal placodes. Construction of quail-chick chimaeras has provided significant information on the migration and fate of the neural crest and placodal cells. Transplantation of neural crest tissue to various sites in these chimaeras has demonstrated that the differentiation of neural crest cells is controlled by environmental influences during their migration and, particularly, during gangliogenesis. Experiments with in vitro and monoclonal antibody techniques have shown that these environmental cues act on a heterogeneous population of neural crest cells whose developmental potencies are partly restricted to definite differentiation pathways.  相似文献   

4.
The evolutionarily conserved Wnt/Wingless signal transduction pathway directs cell proliferation, cell fate, and cell death during development in metazoans and is inappropriately activated in several types of cancer. The majority of colorectal carcinomas contain truncating mutations in the adenomatous polyposis coli (APC) tumor suppressor, a negative regulator of Wnt/Wingless signaling. Here, we demonstrate that Drosophila Apc homologs also have an activating role in both physiological and ectopic Wingless signaling. The Apc amino terminus is important for its activating function, whereas the beta-catenin binding sites are dispensable. Apc likely promotes Wingless transduction through down-regulation of Axin, a negative regulator of Wingless signaling. Given the evolutionary conservation of APC in Wnt signal transduction, an activating role may also be present in vertebrates with relevance to development and cancer.  相似文献   

5.
Commitment of neural crest cells to the sensory neuron lineage   总被引:10,自引:0,他引:10  
Clonal cultures and monoclonal antibodies against a lineage-specific epitope, stage-specific embryonic antigen-1 (SSEA-1) were used to analyze the commitment of quail neural crest cells to the sensory neuron pathway. There were two distinct populations of sensory cells at the time of gangliogenesis. Postmitotic neuroblasts that remained in close association with the neural tube coexisted with a large number of pluripotent cells that formed the leading edge of the emigrating cells and gave rise to sensory and autonomic neuroblasts and to melanocytes. The data suggest a dual origin of spinal sensory neuroblasts and a predominantly late divergence of the autonomic and sensory lineages.  相似文献   

6.
Multiple signaling pathways, including Wnt signaling, participate in animal development, stem cell biology, and human cancer. Although many components of the Wnt pathway have been identified, unresolved questions remain as to the mechanism by which Wnt binding to its receptors Frizzled and Low-density lipoprotein receptor-related protein 6 (LRP6) triggers downstream signaling events. With live imaging of vertebrate cells, we show that Wnt treatment quickly induces plasma membrane-associated LRP6 aggregates. LRP6 aggregates are phosphorylated and can be detergent-solubilized as ribosome-sized multiprotein complexes. Phospho-LRP6 aggregates contain Wnt-pathway components but no common vesicular traffic markers except caveolin. The scaffold protein Dishevelled (Dvl) is required for LRP6 phosphorylation and aggregation. We propose that Wnts induce coclustering of receptors and Dvl in LRP6-signalosomes, which in turn triggers LRP6 phosphorylation to promote Axin recruitment and beta-catenin stabilization.  相似文献   

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Transforming growth factor-beta (TGF-beta) and TGF-beta-related proteins, such as the bone morphogenetic proteins, have emerged as key regulators of stem cell renewal and differentiation. These proteins have disparate roles in regulating the biology of embryonic stem cells and tumor suppression, and they help define the selection of cell fate and the progression of differentiation along a lineage. Here we illustrate their roles in embryonic stem cells and in the differentiation of neural, hematopoietic, mesenchymal, and gastrointestinal epithelial stem cells.  相似文献   

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12.
Inhibition of adipogenesis by Wnt signaling   总被引:1,自引:0,他引:1  
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13.
A stem cell molecular signature   总被引:2,自引:0,他引:2  
Mechanisms regulating self-renewal and cell fate decisions in mammalian stem cells are poorly understood. We determined global gene expression profiles for mouse and human hematopoietic stem cells and other stages of the hematopoietic hierarchy. Murine and human hematopoietic stem cells share a number of expressed gene products, which define key conserved regulatory pathways in this developmental system. Moreover, in the mouse, a portion of the genetic program of hematopoietic stem cells is shared with embryonic and neural stem cells. This overlapping set of gene products represents a molecular signature of stem cells.  相似文献   

14.
Cellular and molecular mechanisms underlying differences in beak morphology likely involve interactions among multiple embryonic populations. We exchanged neural crest cells destined to participate in beak morphogenesis between two anatomically distinct species. Quail neural crest cells produced quail beaks in duck hosts and duck neural crest produced duck bills in quail hosts. These transformations involved morphological changes to non-neural crest host beak tissues. To achieve these changes, donor neural crest cells executed autonomous molecular programs and regulated gene expression in adjacent host tissues. Thus, neural crest cells are a source of molecular information that generates interspecific variation in beak morphology.  相似文献   

15.
Song X  Zhu CH  Doan C  Xie T 《Science (New York, N.Y.)》2002,296(5574):1855-1857
How stem cells are recruited to and maintained in their niches is crucial to understanding their regulation and use in regenerative medicine. Here, we demonstrate that DE-cadherin-mediated cell adhesion is required for anchoring germline stem cells (GSCs) in their niches in the Drosophila ovary. Two major components of this adhesion process, DE-cadherin and Armadillo/beta-catenin, accumulate at high levels in the junctions between GSCs and cap cells, one of the niche components. Removal of these proteins from GSCs results in stem cell loss. Furthermore, DE-cadherin is required for recruiting GSCs to their niche. Our study demonstrates that anchorage of GSCs in their niche by DE-cadherin-mediated adhesion is important for stem cell maintenance and function.  相似文献   

16.
Cranial neural crest cells generate the distinctive bone and connective tissues in the vertebrate head. Classical models of craniofacial development argue that the neural crest is prepatterned or preprogrammed to make specific head structures before its migration from the neural tube. In contrast, recent studies in several vertebrates have provided evidence for plasticity in patterning neural crest populations. Using tissue transposition and molecular analyses in avian embryos, we reconcile these findings by demonstrating that classical manipulation experiments, which form the basis of the prepatterning model, involved transplantation of a local signaling center, the isthmic organizer. FGF8 signaling from the isthmus alters Hoxa2 expression and consequently branchial arch patterning, demonstrating that neural crest cells are patterned by environmental signals.  相似文献   

17.
The regenerative potential of skeletal muscle declines with age, and this impairment is associated with an increase in tissue fibrosis. We show that muscle stem cells (satellite cells) from aged mice tend to convert from a myogenic to a fibrogenic lineage as they begin to proliferate and that this conversion is mediated by factors in the systemic environment of the old animals. We also show that this lineage conversion is associated with an activation of the canonical Wnt signaling pathway in aged myogenic progenitors and can be suppressed by Wnt inhibitors. Furthermore, components of serum from aged mice that bind to the Frizzled family of proteins, which are Wnt receptors, may account for the elevated Wnt signaling in aged cells. These results indicate that the Wnt signaling pathway may play a critical role in tissue-specific stem cell aging and an increase in tissue fibrosis with age.  相似文献   

18.
Augmented Wnt signaling in a mammalian model of accelerated aging   总被引:1,自引:0,他引:1  
The contribution of stem and progenitor cell dysfunction and depletion in normal aging remains incompletely understood. We explored this concept in the Klotho mouse model of accelerated aging. Analysis of various tissues and organs from young Klotho mice revealed a decrease in stem cell number and an increase in progenitor cell senescence. Because klotho is a secreted protein, we postulated that klotho might interact with other soluble mediators of stem cells. We found that klotho bound to various Wnt family members. In a cell culture model, the Wnt-klotho interaction resulted in the suppression of Wnt biological activity. Tissues and organs from klotho-deficient animals showed evidence of increased Wnt signaling, and ectopic expression of klotho antagonized the activity of endogenous and exogenous Wnt. Both in vitro and in vivo, continuous Wnt exposure triggered accelerated cellular senescence. Thus, klotho appears to be a secreted Wnt antagonist and Wnt proteins have an unexpected role in mammalian aging.  相似文献   

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Planarian flatworms can regenerate heads at anterior-facing wounds and tails at posterior-facing wounds throughout the body. How this regeneration polarity is specified has been a classic problem for more than a century. We identified a planarian gene, Smed-betacatenin-1, that controls regeneration polarity. Posterior-facing blastemas regenerate a head instead of a tail in Smed-betacatenin-1(RNAi) animals. Smed-betacatenin-1 is required after wounding and at any posterior-facing wound for polarity. Additionally, intact Smed-betacatenin-1(RNAi) animals display anteriorization during tissue turnover. Five Wnt genes and a secreted Frizzled-related Wnt antagonist-like gene are expressed in domains along the anteroposterior axis that reset to new positions during regeneration, which suggests that Wnts control polarity through Smed-betacatenin-1. Our data suggest that beta-catenin specifies the posterior character of the anteroposterior axis throughout the Bilateria and specifies regeneration polarity in planarians.  相似文献   

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