Precise temporal control of neuroblast migration through combined regulation and feedback of a Wnt receptor
- University Medical Center Utrecht, Netherlands
- Purdue University West Lafayette, United States
- l'Ecole Normale Supérieure, CNRS, INSERM, France
- 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
Euclides E Fernandes Póvoa
Hendrik C Korswagen
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.
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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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
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