Dermal appendage-dependent patterning of zebrafish atoh1a+ Merkel cells

Abstract

Touch system function requires precise interactions between specialized skin cells and somatosensory axons, as exemplified by the vertebrate mechanosensory Merkel cell-neurite complex. Development and patterning of Merkel cells and associated neurites during skin organogenesis remains poorly understood, partly due to the in utero development of mammalian embryos. Here, we discover Merkel cells in the zebrafish epidermis and identify Atonal homolog 1a (Atoh1a) as a marker of zebrafish Merkel cells. We show that zebrafish Merkel cells derive from basal keratinocytes, express neurosecretory and mechanosensory machinery, extend actin-rich microvilli, and complex with somatosensory axons, all hallmarks of mammalian Merkel cells. Merkel cells populate all major adult skin compartments, with region-specific densities and distribution patterns. In vivo photoconversion reveals that Merkel cells undergo steady loss and replenishment during skin homeostasis. Merkel cells develop concomitant with dermal appendages along the trunk and loss of Ectodysplasin signaling, which prevents dermal appendage formation, reduces Merkel cell density by affecting cell differentiation. By contrast, altering dermal appendage morphology changes the distribution, but not density, of Merkel cells. Overall, our studies provide insights into touch system maturation during skin organogenesis and establish zebrafish as an experimentally accessible in vivo model for the study of Merkel cell biology.

Data availability

All data generated or analyses during this study are included in the manuscript and supporting files. Source data files have been provided as indicated.

Article and author information

Author details

  1. Tanya L Brown

    Department of Biology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Emma C Horton

    BiologyDepartment of Biology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9730-7380
  3. Evan W Craig

    Department of Biology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Camille EA Goo

    Department of Biology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9118-4006
  5. Erik C Black

    Department of Biology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2333-8923
  6. Madeleine N Hewitt

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4387-327X
  7. Nathaniel G Yee

    Department of Biology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Everett T Fan

    Department of Biology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. David W Raible

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5342-5841
  10. Jeffrey P Rasmussen

    Department of Biology, University of Washington, Seattle, United States
    For correspondence
    rasmuss@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6997-3773

Funding

National Science Foundation (2011008)

  • Tanya L Brown

National Science Foundation (DGE-2140004)

  • Emma C Horton

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD107108)

  • Jeffrey P Rasmussen

University of Washington Research Royalty Fund (A153025)

  • Jeffrey P Rasmussen

Cancer Consortium

  • Jeffrey P Rasmussen

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 zebrafish experiments were approved by the Institutional Animal Care and Use Committee at the University of Washington (Protocol: #4439-01).

Reviewing Editor

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

Publication history

  1. Received: December 28, 2022
  2. Accepted: January 11, 2023
  3. Accepted Manuscript published: January 17, 2023 (version 1)

Copyright

© 2023, Brown 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. Tanya L Brown
  2. Emma C Horton
  3. Evan W Craig
  4. Camille EA Goo
  5. Erik C Black
  6. Madeleine N Hewitt
  7. Nathaniel G Yee
  8. Everett T Fan
  9. David W Raible
  10. Jeffrey P Rasmussen
(2023)
Dermal appendage-dependent patterning of zebrafish atoh1a+ Merkel cells
eLife 12:e85800.
https://doi.org/10.7554/eLife.85800

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