Regulation of neural crest formation by Pou5f transcription factors

Project Summary/Abstract Neural crest stem cells play a central role in vertebrates as they contribute numerous critical cell types to the body plan including much of the peripheral nervous system and craniofacial skeleton. Accordingly, understanding the molecular mechanisms controlling formation and development of these cells is key to understanding congenital defects, and for regenerative medicine. Pou family transcription factors, particularly the Pou5 and Pou3 subfamilies, play crucial roles in regulating pluripotency, differentiation, and various developmental processes across species. We have recently shown that Pou5 family factors are essential for neural crest formation. Evidence suggests that pou5 evolved from a pou3-like ancestor that was involved in neurogenesis, a function probably ancestral for chordates and therefore one that preceded the origin of pou5 function in the neural crest. The work proposed here will address the differences that have arisen in extant pou5 and pou3 proteins that underlie their distinct activities and targets. The proposed research will advance our understanding of neural crest cells, and provide a new framework with which to understand their origins and stem cell attributes, in addition to shedding light on the molecular underpinnings of a broad set of congenital defects. They will also serve as a paradigm for understanding the evolution of gene regulatory networks by duplication and divergence of key transcription factors.