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  • The EMBO Journal advance online publication 22 October 2009; doi:10.1038/emboj.2009.313

Self-regulation of Stat3 activity coordinates cell-cycle progression and neural crest specification

Massimo Nichane1,2, Xi Ren1,2 and Eric J Bellefroid1

  1. Laboratoire d'Embryologie Moléculaire, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles, Gosselies, Belgium

Correspondence to:

Eric J Bellefroid, Laboratoire d'Embryologie Moléculaire, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles, rue des Profs. Jeener et Brachet 12, Gosselies 6041, Belgium. Tel.:+32 2 650 9732; Fax:+32 2 650 9733; E-mail: ebellefr@ulb.ac.be

Massimo Nichane, Laboratoire d'Embryologie Moléculaire, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles, rue des Profs. Jeener et Brachet 12, Gosselies 6041, Belgium. E-mail: Massimo.Nichane@ulb.ac.be

2These authors contributed equally to this work

Received 29 January 2009; Accepted 25 September 2009

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.

  • Keywords:

    • FGF,
    • neural crest,
    • self-regulation,
    • Stat3,
    • Xenopus