1. Developmental Biology
  2. Evolutionary Biology
Download icon

Wnt/β-catenin regulates an ancient signaling network during zebrafish scale development

  1. Andrew J Aman
  2. Alexis N Fulbright
  3. David M Parichy  Is a corresponding author
  1. University of Virginia, United States
  2. Huntsman Cancer Institute, United States
Research Article
  • Cited 15
  • Views 5,000
  • Annotations
Cite this article as: eLife 2018;7:e37001 doi: 10.7554/eLife.37001


Understanding how patterning influences cell behaviors to generate three dimensional morphologies is a central goal of developmental biology. Additionally, comparing these regulatory mechanisms among morphologically diverse tissues allows for rigorous testing of evolutionary hypotheses. Zebrafish skin is endowed with a coat of precisely patterned bony scales. We use in-toto live imaging during scale development and manipulations of cell signaling activity to elucidate core features of scale patterning and morphogenesis. These analyses show that scale development requires the concerted activity of Wnt/β-catenin, Ectodysplasin (Eda) and Fibroblast growth factor (Fgf) signaling. This regulatory module coordinates Hedgehog (HH) dependent collective cell migration during epidermal invagination, a cell behavior not previously implicated in skin appendage morphogenesis. Our analyses demonstrate the utility of zebrafish scale development as a tractable system in which to elucidate mechanisms of developmental patterning and morphogenesis, and suggest a single, ancient origin of skin appendage patterning mechanisms in vertebrates.

Article and author information

Author details

  1. Andrew J Aman

    Department of Biology and Department of Cell Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Alexis N Fulbright

    University of Utah, Huntsman Cancer Institute, Salt Lake Cite, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5634-4094
  3. David M Parichy

    Department of Biology and Department of Cell Biology, University of Virginia, Charlottesville, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2771-6095


National Institutes of Health (R35 GM122471)

  • David M Parichy

Royalty Research Fund (A112414)

  • David M Parichy

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved Animal Care and Use Committee (ACUC) protocols (#4170) of the University of Virginia. All imaging and regeneration experiments were performed under MS222 anesthesi , and every effort was made to minimize suffering.

Reviewing Editor

  1. Richard M White, Memorial Sloan Kettering Cancer Center, United States

Publication history

  1. Received: March 26, 2018
  2. Accepted: June 21, 2018
  3. Accepted Manuscript published: July 17, 2018 (version 1)
  4. Version of Record published: August 2, 2018 (version 2)


© 2018, Aman 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.


  • 5,000
    Page views
  • 631
  • 15

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Developmental Biology
    2. Genetics and Genomics
    Jason W Millington et al.
    Research Article

    Nutrient-dependent body size plasticity differs between the sexes in most species, including mammals. Previous work in Drosophila showed that body size plasticity was higher in females, yet the mechanisms underlying increased female body size plasticity remain unclear. Here, we discover that a protein-rich diet augments body size in females and not males because of a female-biased increase in activity of the conserved insulin/insulin-like growth factor signaling pathway (IIS). This sex-biased upregulation of IIS activity was triggered by a diet-induced increase in stunted mRNA in females, and required Drosophila insulin-like peptide 2, illuminating new sex-specific roles for these genes. Importantly, we show that sex determination gene transformer promotes the diet-induced increase in stunted mRNA via transcriptional coactivator Spargel to regulate the male-female difference in body size plasticity. Together, these findings provide vital insight into conserved mechanisms underlying the sex difference in nutrient-dependent body size plasticity.

    1. Developmental Biology
    Shiri Kult et al.
    Research Article

    The mechanical challenge of attaching elastic tendons to stiff bones is solved by the formation of a unique transitional tissue. Here, we show that murine tendon-to-bone attachment cells are bi-fated, activating a mixture of chondrocyte and tenocyte transcriptomes, under regulation of shared regulatory elements and Krüppel-like factors (KLFs) transcription factors. High-throughput bulk and single-cell RNA sequencing of humeral attachment cells revealed expression of hundreds of chondrogenic and tenogenic genes, which was validated by in situ hybridization and single-molecule ISH. ATAC sequencing showed that attachment cells share accessible intergenic chromatin areas with either tenocytes or chondrocytes. Epigenomic analysis revealed enhancer signatures for most of these regions. Transgenic mouse enhancer reporter assays verified the shared activity of some of these enhancers. Finally, integrative chromatin and motif analyses and transcriptomic data implicated KLFs as regulators of attachment cells. Indeed, blocking expression of both Klf2 and Klf4 in developing limb mesenchyme impaired their differentiation.