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Requirement for Foxd3 in the maintenance of neural crest progenitors.

Understanding the molecular mechanisms of stem cell maintenance is crucial for the ultimate goal of manipulating stem cells for the treatment of disease. Foxd3 is required early in mouse embryogenesis; Foxd3(-/-) embryos fail around the time of implantation, cells of the inner cell mass cannot be maintained in vitro, and blastocyst-derived stem cell lines cannot be established. Here, we report that Foxd3 is required for maintenance of the multipotent mammalian neural crest. Using tissue-specific deletion of Foxd3 in the neural crest, we show that Foxd3(flox/-); Wnt1-Cre mice die perinatally with a catastrophic loss of neural crest-derived structures. Cranial neural crest tissues are either missing or severely reduced in size, the peripheral nervous system consists of reduced dorsal root ganglia and cranial nerves, and the entire gastrointestinal tract is devoid of neural crest derivatives. These results demonstrate a global role for this transcriptional repressor in all aspects of neural crest maintenance along the anterior-posterior axis, and establish an unprecedented molecular link between multiple divergent progenitor lineages of the mammalian embryo.

Pubmed ID: 18367558 RIS Download

Mesh terms: Animals | Body Patterning | Cell Death | Cell Differentiation | Cell Movement | Cell Proliferation | Forkhead Transcription Factors | Mice | Multipotent Stem Cells | Mutation | Neural Crest | Peripheral Nervous System | Repressor Proteins | Wnt1 Protein

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Associated grants

  • Agency: NICHD NIH HHS, Id: R01 HD036720-10
  • Agency: NICHD NIH HHS, Id: HD36720
  • Agency: NICHD NIH HHS, Id: R01 HD036720
  • Agency: NICHD NIH HHS, Id: R01 HD036720-08
  • Agency: NICHD NIH HHS, Id: R01 HD036720-09
  • Agency: NICHD NIH HHS, Id: R01 HD036720-07
  • Agency: NICHD NIH HHS, Id: R01 HD036720-11
  • Agency: NICHD NIH HHS, Id: R01 HD036720-06

Mouse Genome Informatics (Data, Gene Annotation)

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