| Self-regulation of Stat3 activity coordinates cell-cycle progression and neural crest specification. | |
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MedLine Citation:
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PMID: 19851287 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Massimo Nichane; Xi Ren; Eric J Bellefroid |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-10-22 |
Journal Detail:
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Title: The EMBO journal Volume: 29 ISSN: 1460-2075 ISO Abbreviation: EMBO J. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-06 Completed Date: 2010-02-01 Revised Date: 2011-07-20 |
Medline Journal Info:
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Nlm Unique ID: 8208664 Medline TA: EMBO J Country: England |
Other Details:
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Languages: eng Pagination: 55-67 Citation Subset: IM |
Affiliation:
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Laboratoire d'Embryologie Moléculaire, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Basic Helix-Loop-Helix Transcription Factors / genetics, metabolism Cell Cycle / genetics, physiology* Cell Differentiation Cell Proliferation Cell Survival Embryonic Stem Cells / cytology, metabolism Fibroblast Growth Factors / genetics, metabolism Gene Expression Regulation, Developmental Inhibitor of Differentiation Proteins / genetics, metabolism Models, Biological Neural Crest / cytology, embryology*, metabolism* Oligodeoxyribonucleotides, Antisense / genetics Receptor, Fibroblast Growth Factor, Type 4 / genetics, metabolism Recombinant Proteins / genetics, metabolism STAT3 Transcription Factor / genetics, metabolism* Signal Transduction Xenopus / embryology*, genetics, metabolism* Xenopus Proteins / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Basic Helix-Loop-Helix Transcription Factors; 0/Id3 protein, Xenopus; 0/Inhibitor of Differentiation Proteins; 0/Oligodeoxyribonucleotides, Antisense; 0/Recombinant Proteins; 0/STAT3 Transcription Factor; 0/Xenopus Proteins; 0/hairy2 protein, Xenopus; 62031-54-3/Fibroblast Growth Factors; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 4 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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