Progenitors oppositely polarize WNT activators and inhibitors to orchestrate tissue development
- The Rockefeller University, United States
- Broad Institute of MIT and Harvard, United States
- The Francis Crick Institute, United Kingdom
- Howard Hughes Medical Institute, The Rockefeller University, United States
Abstract
To spatially co-exist and differentially specify fates within developing tissues, morphogenetic cues must be correctly positioned and interpreted. Here, we investigate mouse hair follicle development to understand how morphogens operate within closely spaced, fate-diverging progenitors. Coupling transcriptomics with genetics, we show that emerging hair progenitors produce both WNTs and WNT inhibitors. Surprisingly, however, instead of generating a negative feedback loop, the signals oppositely polarize, establishing sharp boundaries and consequently a short-range morphogen gradient that we show is essential for three-dimensional pattern formation. By establishing a morphogen gradient at the cellular level, signals become constrained. The progenitor preserves its WNT signaling identity and maintains WNT signaling with underlying mesenchymal neighbors, while its overlying epithelial cells become WNT-restricted. The outcome guarantees emergence of adjacent distinct cell types to pattern the tissue.
Data availability
RNA sequencing data have been deposited in the Gene Expression Omnibus under accession number GSE108745
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WNT-signaling cells polarize inhibitors to protect their identity and fateNCBI Gene Expression Omnibus, GSE108745.
Article and author information
Author details
Tamara Ouspenskaia
Funding
National Institutes of Health (R01-AR31737)
- Elaine Fuchs
National Institutes of Health (R37-AR27883)
- Elaine Fuchs
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Valerie Horsley, Yale University, United States
Ethics
Animal experimentation: All animal procedures used in this study are described in our #17020-H protocol named Development and Differentiation in the Skin, which had been previously reviewed and approved by the Rockefeller University Institutional Animal Care and Use Committee (IACUC).
Version history
- Received: December 9, 2019
- Accepted: April 17, 2020
- Accepted Manuscript published: April 20, 2020 (version 1)
- Version of Record published: May 14, 2020 (version 2)
Copyright
© 2020, Matos 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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Progenitors oppositely polarize WNT activators and inhibitors to orchestrate tissue development
eLife 9:e54304.
https://doi.org/10.7554/eLife.54304
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