Precise temporal control of neuroblast migration through combined regulation and feedback of a Wnt receptor

  1. Erik S Schild
  2. Shivam Gupta
  3. Clément Dubois
  4. Euclides E Fernandes Póvoa
  5. Marie-Anne Félix
  6. Andrew Mugler  Is a corresponding author
  7. Hendrik C Korswagen  Is a corresponding author
  1. University Medical Center Utrecht, Netherlands
  2. Purdue University West Lafayette, United States
  3. l'Ecole Normale Supérieure, CNRS, INSERM, France
  4. University of Pittsburgh, United States

Abstract

Many developmental processes depend on precise temporal control of gene expression. We have previously established a theoretical framework for regulatory strategies that can govern such high temporal precision, but experimental validation of these predictions was still lacking. Here, we use the time-dependent expression of a Wnt receptor that controls neuroblast migration in C. elegans as a tractable system to study a robust, cell-intrinsic timing mechanism in vivo. Single molecule mRNA quantification showed that the expression of the receptor increases non-linearly, a dynamic that is predicted to enhance timing precision over an unregulated, linear increase in timekeeper abundance. We show that this upregulation depends on transcriptional activation, providing in vivo evidence for a model in which the timing of receptor expression is regulated through an accumulating activator that triggers expression when a specific threshold is reached. This timing mechanism acts across a cell division that occurs in the neuroblast lineage, and is influenced by the asymmetry of the division. Finally, we show that positive feedback of receptor expression through the canonical Wnt pathway enhances temporal precision. We conclude that robust cell-intrinsic timing can be achieved by combining regulation and feedback of the timekeeper gene.

Data availability

All data generated or analysed during this study are included in the manuscript and figures. Source datafiles containing the numerical data used to generate the figures can be accessed at https://github.com/erikschild/mig 1_timer_code

Article and author information

Author details

  1. Erik S Schild

    Hubrecht Institute, University Medical Center Utrecht, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Shivam Gupta

    Department of Physics and Astronomy, Purdue University West Lafayette, West Lafayette, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Clément Dubois

    l'Ecole Normale Supérieure, CNRS, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Euclides E Fernandes Póvoa

    Hubrecht Institute, University Medical Center Utrecht, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0920-7783
  5. Marie-Anne Félix

    l'Ecole Normale Supérieure, CNRS, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Andrew Mugler

    Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, United States
    For correspondence
    andrew.mugler@pitt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9367-7026
  7. Hendrik C Korswagen

    Hubrecht Institute, University Medical Center Utrecht, Utrecht, Netherlands
    For correspondence
    r.korswagen@hubrecht.eu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7931-4472

Funding

Human Frontier Science Program (RGP0030/2016)

  • Marie-Anne Félix
  • Andrew Mugler
  • Hendrik C Korswagen

National Science Foundation (PHY-1945018)

  • Shivam Gupta
  • Andrew Mugler

Simons Foundation (376198)

  • Shivam Gupta
  • Andrew Mugler

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

Reviewing Editor

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

Version history

  1. Received: August 12, 2022
  2. Preprint posted: October 26, 2022 (view preprint)
  3. Accepted: May 12, 2023
  4. Accepted Manuscript published: May 15, 2023 (version 1)
  5. Version of Record published: June 7, 2023 (version 2)

Copyright

© 2023, Schild 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. Erik S Schild
  2. Shivam Gupta
  3. Clément Dubois
  4. Euclides E Fernandes Póvoa
  5. Marie-Anne Félix
  6. Andrew Mugler
  7. Hendrik C Korswagen
(2023)
Precise temporal control of neuroblast migration through combined regulation and feedback of a Wnt receptor
eLife 12:e82675.
https://doi.org/10.7554/eLife.82675

Share this article

https://doi.org/10.7554/eLife.82675

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