PROJECT SUMMARY ABSTRACT The goal of this project is to define the molecular mechanisms governing neural crest development. Neural crest cells (NCC) are a highly migratory and multipotent cell population that gives rise to an incredible diversity of differentiated cell types. During mammalian development, NCCs are induced from pluripotent ectoderm at the lateral margins of the developing neural plate. The molecular mechanisms regulating mammalian neural crest induction are poorly understood. In this project, we focus on a highly expressed microRNA family in pluripotency, miR-302, which plays a critical role during mammalian neural crest induction. Using genetic loss- of-function mouse and human models, we find that miR-302 is required to prevent precocious neural crest specification. Additionally, we present data suggesting that miR-302 regulates the timing of neural crest development by targeting and repressing several novel factors. This project will provide insight into the earliest stages of mammalian neural crest development and shed light on the developmental relationship between ectodermal pluripotency and neural crest multipotency.