Dermal appendage-dependent patterning of zebrafish atoh1a+ Merkel cells
- University of Washington, United States
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
Madeleine N Hewitt
Jeffrey P Rasmussen
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
- Marianne E Bronner, California Institute of Technology, United States
Version history
- Preprint posted: August 11, 2022 (view preprint)
- Received: December 28, 2022
- Accepted: January 11, 2023
- Accepted Manuscript published: January 17, 2023 (version 1)
- Version of Record published: February 6, 2023 (version 2)
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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Dermal appendage-dependent patterning of zebrafish atoh1a+ Merkel cells
eLife 12:e85800.
https://doi.org/10.7554/eLife.85800
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