04-P014 Stat3 self-regulates its activity downstream of fibroblast growth factors to coordinate cell cycle progression and specification of neural crest

A complex set of extracellular signals is required for neural crest (NC) specification. However, how these signals function to coordinate cell cycle progression and differentiation remains poorly understood. Here,we report inXenopus a role forStat3 inthis process downstream of FGF signaling. Depletion of Stat3 inhibited NC gene expression and proliferation while its overexpression expanded the NC domain and promoted cell proliferation. Stat3 was phosphorylated and activated in ectodermal cells by FGFs through FGFR4 binding. Stat3 activation was also modulated at the protein level by the transcription factors Hairy2 and Id3, Hairy2 facilitating and Id3 disrupting Stat3–FGFR4 complex formation. Furthermore, Hairy2 and Id3 expression were found to be under opposite transcriptional control by distinct levels of Stat3. Finally, the level of Stat3 activity was found also to critically regulate NC cell fate and proliferation, low levels inducing cell proliferation and differentiation and high levels promoting the maintenance of cells in an undifferentiated state.Together, our data indicate that Stat3, downstream of FGFs and under the positive and negative feedback regulation of Hairy2 and Id3, plays an essential role in the coordination of cell cycle progression and differentiation during NC specification.