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Regulation of Multipotency in the Neural Crest
Author(s) -
Labosky Patricia Ann,
Mundell Nathan A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.180.1
Subject(s) - neural crest , progenitor cell , microbiology and biotechnology , biology , multipotent stem cell , cell fate determination , fate mapping , mesenchymal stem cell , neural stem cell , stem cell , progenitor , embryo , genetics , transcription factor , gene
Neural crest (NC) progenitors generate a wide array of cell types, yet the molecules controlling NC multipotency and self‐renewal are poorly understood. Likewise, factors mediating cell‐intrinsic distinctions between multipotent versus fate‐restricted (bi‐potent vs tri‐potent) progenitors have not been identified. Our earlier work demonstrated that Foxd3 is required for maintenance of multipotent NC progenitors in the mouse embryo. Here, we have used a well‐defined in vitro explant system to demonstrate that Foxd3 mediates a fate restriction choice for NCSCs; loss of Foxd3 biases individual multipotent NC cells toward a mesenchymal fate with a concomitant loss of neural potential. This cell fate switch was conserved in the embryo with cranial NC preciously upregulating markers of mesenchymal differentiation. More posteriorly, neural NC derivatives were preferentially lost in Foxd3 mutant embryos while abnormally‐fated NC‐derived vascular smooth muscle cells were located ectopically in the aorta, demonstrating an inability of these cells to recognize their ultimate migration targets. These results, for the first time, demonstrate that neural potential can be separated from NCSC multipotency by the action of a single gene. Our results draw novel parallels between NC and other progenitor populations that depend on this functionally conserved stem cell protein to regulate self‐renewal and multipotency. This work was supported by an NIH R01 HD36720 to PAL and an NIH F31NS065604 and an AHA Predoctoral Fellowship 0615209B to NAM.