Progenitors oppositely polarize WNT activators and inhibitors to orchestrate tissue development

  1. Irina Matos
  2. Amma Asare
  3. John Levorse
  4. Tamara Ouspenskaia
  5. June de la Cruz-Racelis
  6. Laura-Nadine Schuhmacher
  7. Elaine Fuchs  Is a corresponding author
  1. The Rockefeller University, United States
  2. Broad Institute of MIT and Harvard, United States
  3. The Francis Crick Institute, United Kingdom
  4. 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

The following data sets were generated

Article and author information

Author details

  1. Irina Matos

    Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6100-8020
  2. 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.
  3. John Levorse

    Robin Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, United States
    Competing interests
    No competing interests declared.
  4. Tamara Ouspenskaia

    KCO, Broad Institute of MIT and Harvard, Cambridge, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5462-7103
  5. 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.
  6. Laura-Nadine Schuhmacher

    Epithelial Cell Interactions Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    No competing interests declared.
  7. 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.
    ORCID icon "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).

Reviewing Editor

  1. Valerie Horsley, Yale University, United States

Publication history

  1. Received: December 9, 2019
  2. Accepted: April 17, 2020
  3. Accepted Manuscript published: April 20, 2020 (version 1)
  4. 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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  1. Irina Matos
  2. Amma Asare
  3. John Levorse
  4. Tamara Ouspenskaia
  5. June de la Cruz-Racelis
  6. Laura-Nadine Schuhmacher
  7. Elaine Fuchs
(2020)
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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