1. Developmental Biology
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Cytoplasmic NOTCH and membrane-derived β-catenin link cell fate choice to epithelial-mesenchymal transition during myogenesis

  1. Daniel Sieiro
  2. Anne C Rios
  3. Claire E Hirst
  4. Christophe Marcelle  Is a corresponding author
  1. Monash University, Australia
Research Article
  • Cited 19
  • Views 2,709
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Cite this article as: eLife 2016;5:e14847 doi: 10.7554/eLife.14847

Abstract

How cells in the embryo coordinate epithelial plasticity with cell fate decision in a fast changing cellular environment is largely unknown. In chick embryos, skeletal muscle formation is initiated by migrating Delta1-expressing neural crest cells that trigger NOTCH signaling and myogenesis in selected epithelial somite progenitor cells, which rapidly translocate into the nascent muscle to differentiate. Here, we uncovered at the heart of this response a signaling module encompassing NOTCH, GSK-3βSNAI1 and β-catenin. Independent of its transcriptional function, NOTCH profoundly inhibits GSK-3βactivity. As a result SNAI1 is stabilized, triggering an epithelial to mesenchymal transition. This allows the recruitment of β-catenin from the membrane, which acts as a transcriptional co-factor to activate myogenesis, independently of WNT ligand. Our results intimately associate the initiation of myogenesis to a change in cell adhesion and may reveal a general principle for coupling cell fate changes to EMT in many developmental and pathological processes.

Article and author information

Author details

  1. Daniel Sieiro

    Australian Regenerative Medicine Institute, Monash University, Clayton, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Anne C Rios

    Australian Regenerative Medicine Institute, Monash University, Clayton, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Claire E Hirst

    Australian Regenerative Medicine Institute, Monash University, Clayton, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Christophe Marcelle

    Australian Regenerative Medicine Institute, Monash University, Clayton, Australia
    For correspondence
    christophe.marcelle@monash.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Publication history

  1. Received: January 29, 2016
  2. Accepted: May 23, 2016
  3. Accepted Manuscript published: May 24, 2016 (version 1)
  4. Accepted Manuscript updated: June 2, 2016 (version 2)
  5. Version of Record published: June 22, 2016 (version 3)

Copyright

© 2016, Sieiro et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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