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EMBO J 2010 Jan 06;291:55-67. doi: 10.1038/emboj.2009.313.
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Self-regulation of Stat3 activity coordinates cell-cycle progression and neural crest specification.

Nichane M , Ren X , Bellefroid EJ .

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 in Xenopus a role for the transcription factor signal transducers and activators of transcription-3 (Stat3) in this process downstream of FGF signalling. Depletion of Stat3 inhibits NC gene expression and cell proliferation, whereas overexpression expands the NC domain and promotes cell proliferation. Stat3 is phosphorylated and activated in ectodermal cells by FGFs through binding with FGFR4. Stat3 activation is also modulated by Hairy2 and Id3 proteins that, respectively, facilitate and disrupt Stat3-FGFR4 complex formation. Furthermore, distinct levels of Stat3 activity control Hairy2 and Id3 transcription, leading to Stat3 self-regulation. Finally, high Stat3 activity maintains cells in an undifferentiated state, whereas low activity promotes cell proliferation and NC differentiation. Together, our data suggest 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.

PubMed ID: 19851287
PMC ID: PMC2808363
Article link: EMBO J

Species referenced: Xenopus
Genes referenced: fgfr4 hes4 id3 stat3 stat3.2
Morpholinos: dll1 MO1 fgfr1 MO1 fgfr1 MO2 fgfr4 MO1 fgfr4 MO2 hes4 MO1 hes4 MO2 id3 MO1 stat3.1 MO1

References [+] :
Ahrens, Tissues and signals involved in the induction of placodal Six1 expression in Xenopus laevis. 2005, Pubmed, Xenbase