Deciphering the developmental and evolutionary basis of stem cell pluripotency and the emergence of the vertebrate neural crest

The neural crest is a vertebrate-specific stem cell population that generates many of the cell types and structures that define the vertebrate body plan. By using the neural crest as a model for pluripotency and stem cell development, we can uncover general principles of stem cell biology and gain insights into how gene regulatory networks (GRNs) evolve. Previously work has shown that neural crest “stemness” may have been co-opted from the pluripotency GRN controlling embryonic stem cells in early blastula-stage embryos. However, the regulatory mechanisms controlling this blastula-to-neural crest transition remain unknown. The work proposed here will address this knowledge gap by testing the hypothesis that Snail transcription factors are instrumental in mediating stem cell pluripotency and cell fate decisions in the blastula and neural crest and helped drive the transition from a blastula to neural crest regulatory state across vertebrates. I will take a powerful evolutionary approach by combining studies in a jawed vertebrate, Xenopus laevis, and a basal jawless vertebrate, the sea lamprey. This work will elucidate the unique and shared contributions of Snail factors to control of pluripotency GRNs in neural crest and blastula stem cells, identify the regulatory inputs that control their expression in these cells, and determine the extent to which these features are shared across vertebrates. The proposed aims will provide a platform for tracing the evolutionary origins of stem cells in animals, and how these stem cells contribute to both normal embryonic development and the origin and progression of stem cell-related disease.