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TWIST1 and chromatin regulatory proteins interact to guide neural crest cell differentiation

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Cite this article as: eLife 2021;10:e62873 doi: 10.7554/eLife.62873

Abstract

Protein interaction is critical molecular regulatory activity underlining cellular functions and precise cell fate choices. Using TWIST1 BioID-proximity-labelling and network propagation analyses, we discovered and characterized a TWIST-chromatin regulatory module (TWIST1-CRM) in the neural crest cells (NCC). Combinatorial perturbation of core members of TWIST1-CRM: TWIST1, CHD7, CHD8, and WHSC1 in cell models and mouse embryos revealed that loss of the function of the regulatory module resulted in abnormal differentiation of NCCs and compromised craniofacial tissue patterning. Following NCC delamination, low level of TWIST1-CRM activity is instrumental to stabilize the early NCC signatures and migratory potential by repressing the neural stem cell programs. High level of TWIST1 module activity at later phases commits the cells to the ectomesenchyme. Our study further revealed the functional interdependency of TWIST1 and potential neurocristopathy factors in NCC development.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Sequencing data have been deposited in GEO under accession codes GSE130251. External data analyzed has been listed in Supplementary File 6.

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Article and author information

Author details

  1. Xiaochen Fan

    Embryology, CMRI, The University of Sydney, Sydney, Australia
    For correspondence
    x6fan@eng.ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4316-0616
  2. V Pragathi Masamsetti

    Embryology Unit, CMRI, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Jane QJ Sun

    Embryology Unit, CMRI, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Kasper Engholm-Keller

    Synapse Proteomics Group, CMRI, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Pierre Osteil

    Embryology Unit, CMRI, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Joshua Studdert

    Embryology Unit, CMRI, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Mark E Graham

    Synapse Proteomics, CMRI, The University of Sydney, Westmead, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7290-1217
  8. Nicolas Fossat

    Embryology Unit, CMRI, The University of Sydney, Sydney, Australia
    For correspondence
    nfossat@sund.ku.dk
    Competing interests
    The authors declare that no competing interests exist.
  9. Patrick PL Tam

    Embryology Unit, CMRI, The University of Sydney, Westmead, Australia
    For correspondence
    PTam@cmri.org.au
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Health and Medical Research Council (1066832,1079160,1003100,1110751)

  • Mark E Graham
  • Patrick PL Tam

Australian Research Council (1094008)

  • Xiaochen Fan
  • Patrick PL Tam

University of Sydney

  • Xiaochen Fan

Children's Medical Research Institute

  • Xiaochen Fan
  • Pierre Osteil
  • Nicolas Fossat

Carlsbergfondet (CF15-1056,CF16-0066)

  • Kasper Engholm-Keller

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

Ethics

Animal experimentation: Animal experimentations were performed in compliance with animal ethics and welfare guidelines stipulated by the Children's Medical Research Institute/Children's Hospital at Westmead Animal Ethics Committee, protocol number C230.

Reviewing Editor

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

Publication history

  1. Received: September 7, 2020
  2. Accepted: February 5, 2021
  3. Accepted Manuscript published: February 8, 2021 (version 1)
  4. Version of Record published: March 17, 2021 (version 2)

Copyright

© 2021, Fan 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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