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Molecular Underpinnings of Pluripotency Suggest a Novel Origin for Neural Crest Stem Cells and a New Theory for Evolution of Vertebrates

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Neural crest cells are a population of multipotent stem cells that are unique to vertebrates and give rise to a wide range of derivatives in the developing embryo, including elements of the craniofacial skeleton, pigmentation of the skin and peripheral nervous system. Although these cells reside in the ectoderm, they generate cell types typically categorized as mesodermal, and their broad developmental potential persists past the time when most ectoderm-derived cells have become lineage restricted. We recently proposed a new model for the developmental and evolutionary origins of neural crest cells based on the strikingly conserved molecular underpinnings of potency observed in these cells and pluripotent blastula stem cells. We suggest that neural crest cells may have evolved as a consequence of a subset of pluripotent blastula cells retaining the activity of much of the regulatory network underlying pluripotency through gastrula stages. A striking difference in the regulatory factors expressed in pluripotent blastula cells and neural crest cells is the deployment of different sub-families of Sox transcription factors. Whereas SoxB1 factors are known to play central roles in pluripotent blastula and ES cells, neural crest cells express high levels of SoxE family transcription factors. I explored the role that this molecular “hand-off” of Sox factor activity, from SoxB1 to SoxE, play in the retention of pluripotency and the subsequent biasing of cells to contribute to specific neural crest-derived lineages by probing the shared and distinct activities of these factors in early Xenopus embryos.

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