Progenitors oppositely polarize WNT activators and inhibitors to orchestrate tissue development

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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

The following data sets were generated

1. Irina Matos
2. Elaine Fuchs
(2018) WNT-signaling cells polarize inhibitors to protect their identity and fate
NCBI Gene Expression Omnibus, GSE108745.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108745

Article and author information

Author details

Irina Matos

Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-6100-8020
Amma Asare

Robin Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, United States

Competing interests
No competing interests declared.
John Levorse

Robin Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, United States

Competing interests
No competing interests declared.
Tamara Ouspenskaia

KCO, Broad Institute of MIT and Harvard, Cambridge, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-5462-7103
June de la Cruz-Racelis

Robin Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, The Rockefeller University, United States

Competing interests
No competing interests declared.
Laura-Nadine Schuhmacher

Epithelial Cell Interactions Laboratory, The Francis Crick Institute, London, United Kingdom

Competing interests
No competing interests declared.
Elaine Fuchs

Robin Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States

For correspondence
elaine.fuchs@rockefeller.edu

Competing interests
Elaine Fuchs, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0002-0978-5137

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.

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).

Copyright

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.