Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis

Abstract

A crucial step in cell differentiation is the silencing of developmental programs underlying multipotency. While much is known about how lineage-specific genes are activated to generate distinct cell types, the mechanisms driving suppression of stemness are far less understood. To address this, we examined the regulation of the transcriptional network that maintains progenitor identity in avian neural crest cells. Our results show that a regulatory circuit formed by Wnt, Lin28a and let-7 miRNAs controls the deployment and the subsequent silencing of the multipotency program in a position-dependent manner. Transition from multipotency to differentiation is determined by the topological relationship between the migratory cells and the dorsal neural tube, which acts as a Wnt-producing stem cell niche. Our findings highlight a mechanism that rapidly silences complex regulatory programs, and elucidate how transcriptional networks respond to positional information during cell differentiation.

Data availability

All data generated for this study are included in the manuscript and supporting files. Source data files have been provided for all figures.

Article and author information

Author details

  1. Debadrita Bhattacharya

    Department of Molecular Biology and Genetics,, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Megan Rothstein

    Department of Molecular Biology and Genetics,, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ana Paula Azambuja

    Department of Molecular Biology and Genetics,, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Marcos Simoes-Costa

    Department of Molecular Biology and Genetics,, Cornell University, Ithaca, United States
    For correspondence
    simoescosta@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1452-7068

Funding

National Institute of Dental and Craniofacial Research

  • Marcos Simoes-Costa

March of Dimes Foundation

  • Marcos Simoes-Costa

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

Reviewing Editor

  1. Richard M White, Memorial Sloan Kettering Cancer Center, United States

Publication history

  1. Received: July 28, 2018
  2. Accepted: December 4, 2018
  3. Accepted Manuscript published: December 6, 2018 (version 1)
  4. Version of Record published: December 20, 2018 (version 2)

Copyright

© 2018, Bhattacharya 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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  1. Debadrita Bhattacharya
  2. Megan Rothstein
  3. Ana Paula Azambuja
  4. Marcos Simoes-Costa
(2018)
Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis
eLife 7:e40556.
https://doi.org/10.7554/eLife.40556

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