1. Developmental Biology

Regulation of posterior body and epidermal morphogenesis in Zebrafish by localized Yap1 and Wwtr1

  1. David Kimelman  Is a corresponding author
  2. Natalie L Smith
  3. Jason Kuan Han Lai
  4. Didier YR Stainier
  1. University of Washington, United States
  2. Max Planck Institute for Heart and Lung Research, Germany
https://doi.org/10.7554/eLife.31065
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  1. David Kimelman
  2. Natalie L Smith
  3. Jason Kuan Han Lai
  4. Didier YR Stainier
(2017)
Regulation of posterior body and epidermal morphogenesis in Zebrafish by localized Yap1 and Wwtr1
eLife 6:e31065.
https://doi.org/10.7554/eLife.31065
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Abstract

The vertebrate embryo undergoes a series of dramatic morphological changes as the body extends to form the complete anterior-posterior axis during the somite-forming stages. The molecular mechanisms regulating these complex processes are still largely unknown. We show that the Hippo pathway transcriptional coactivators Yap1 and Wwtr1 are specifically localized to the presumptive epidermis and notochord, and play a critical and unexpected role in posterior body extension by regulating Fibronectin assembly underneath the presumptive epidermis and surrounding the notochord. We further find that Yap1 and Wwtr1, also via Fibronectin, have an essential role in the epidermal morphogenesis necessary to form the initial dorsal and ventral fins, a process previously thought to involve bending of an epithelial sheet, but which we now show involves concerted active cell movement. Our results reveal how the Hippo pathway transcriptional program, localized to two specific tissues, acts to control essential morphological events in the vertebrate embryo.

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Article and author information

Author details

  1. David Kimelman

    Department of Biochemistry, University of Washington, Seattle, United States
    For correspondence
    kimelman@uw.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9261-4506

  2. Natalie L Smith

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.

  3. Jason Kuan Han Lai

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.

  4. Didier YR Stainier

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    Didier YR Stainier, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0382-0026

Funding

National Institutes of Health (GM079203)

  • David Kimelman

Max Planck Society

  • Jason Kuan Han Lai
  • Didier YR Stainier

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

Ethics

Animal experimentation: This study was performed in strict accordance with institutional (UW and MPG) and national ethical and animal welfare guidelines. All of the animals were handled according to approved institutional animal care protocols (Permission No. B2/1068 for DS and IACUC protocol 2387-02 for DK).

Copyright

© 2017, Kimelman 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. David Kimelman
  2. Natalie L Smith
  3. Jason Kuan Han Lai
  4. Didier YR Stainier
(2017)
Regulation of posterior body and epidermal morphogenesis in Zebrafish by localized Yap1 and Wwtr1
eLife 6:e31065.
https://doi.org/10.7554/eLife.31065

Share this article

https://doi.org/10.7554/eLife.31065

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Further reading

    1. Cell Biology
    2. Developmental Biology

    DNA-damage induced cell death in yap1;wwtr1 mutant epidermal basal cells

    Jason KH Lai, Pearlyn JY Toh ... Timothy E Saunders
    Research Advance Updated

    In a previous study, it was reported that Yap1 and Wwtr1 in zebrafish regulates the morphogenesis of the posterior body and epidermal fin fold (Kimelman et al., 2017). We report here that DNA damage induces apoptosis of epidermal basal cells (EBCs) in zebrafish yap1-/-;wwtr1-/- embryos. Specifically, these mutant EBCs exhibit active Caspase-3, Caspase-8, and γH2AX, consistent with DNA damage serving as a stimulus of the extrinsic apoptotic pathway in epidermal cells. Live imaging of zebrafish epidermal cells reveals a steady growth of basal cell size in the developing embryo, but this growth is inhibited in mutant basal cells followed by apoptosis, leading to the hypothesis that factors underscoring cell size play a role in this DNA damage-induced apoptosis phenotype. We tested two of these factors using cell stretching and substrate stiffness assays, and found that HaCaT cells cultured on stiff substrates exhibit more numerous γH2AX foci compared to ones cultured on soft substrates. Thus, our experiments suggest that substrate rigidity may modulate genomic stress in epidermal cells, and that Yap1 and Wwtr1 promotes their survival.