1. Developmental Biology
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An Eya1-Notch axis specifies bipotential epibranchial differentiation in mammalian craniofacial morphogenesis

  1. Haoran Zhang
  2. Li Wang
  3. Elaine Yee Man Wong
  4. Sze Lan Tsang
  5. Pin-Xian Xu
  6. Urban Lendahl
  7. Mai Har Sham  Is a corresponding author
  1. The University of Hong Kong, Hong Kong
  2. Mount Sinai School of Medicine, United States
  3. Karolinska Institute, Sweden
Research Article
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Cite this article as: eLife 2017;6:e30126 doi: 10.7554/eLife.30126

Abstract

Craniofacial morphogenesis requires proper development of pharyngeal arches and epibranchial placodes. We show that the epibranchial placodes, in addition to giving rise to cranial sensory neurons, generate a novel lineage-related non-neuronal cell population for mouse pharyngeal arch development. Eya1 is essential for the development of epibranchial placodes and proximal pharyngeal arches. We identify an Eya1-Notch regulatory axis that specifies both the neuronal and non-neuronal commitment of the epibranchial placode, where Notch acts downstream of Eya1 and promotes the non-neuronal cell fate. Notch is regulated by the threonine phosphatase activity of Eya1. Eya1 dephosphorylates p-threonine-2122 of the Notch1 intracellular domain (Notch1 ICD), which increases the stability of Notch1 ICD and maintains Notch signaling activity in the non-neuronal epibranchial placodal cells. Our data unveil a more complex differentiation program in epibranchial placodes and an important role for the Eya1-Notch axis in craniofacial morphogenesis.

Article and author information

Author details

  1. Haoran Zhang

    School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  2. Li Wang

    School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  3. Elaine Yee Man Wong

    School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  4. Sze Lan Tsang

    School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  5. Pin-Xian Xu

    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Urban Lendahl

    Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Mai Har Sham

    School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
    For correspondence
    mhsham@hku.hk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1179-7839

Funding

Research Grants Council, University Grants Committee (RGC GRF 777411)

  • Mai Har Sham

Research Grants Council, University Grants Committee (RGC GRF 17113415)

  • Mai Har Sham

Cancerfonden (SCS X2017-2019,335)

  • Urban Lendahl

Vetenskapsrådet (project grant 2014-2018,RX331)

  • Urban Lendahl

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All mouse experiments were performed in strict accordance with the recommendations and approved by the University of Hong Kong animal research ethics committee (CULATR No. 3329-14 and 3862-15).

Reviewing Editor

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

Publication history

  1. Received: July 3, 2017
  2. Accepted: November 13, 2017
  3. Accepted Manuscript published: November 15, 2017 (version 1)
  4. Version of Record published: November 28, 2017 (version 2)

Copyright

© 2017, Zhang 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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