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DNA-damage induced cell death in yap1;wwtr1 mutant epidermal basal cells
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Lai, Jason K. H., Toh, Pearlyn J. Y., Cognart, Hamizah A, Chouhan, Geetika and Saunders, Timothy E. (2022) DNA-damage induced cell death in yap1;wwtr1 mutant epidermal basal cells. eLife, 11 . e72302. doi:10.7554/elife.72302 ISSN 2050-084X.
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WRAP-DNA-damage-induced-cell-death-yap1-wwtr1-mutant-epidermal-basal-cells-Saunders-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (14Mb) | Preview |
Official URL: https://doi.org/10.7554/elife.72302
Abstract
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.
| Item Type: | Journal Article | ||||||
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| Subjects: | Q Science > QH Natural history Q Science > QL Zoology Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||
| SWORD Depositor: | Library Publications Router | ||||||
| Library of Congress Subject Headings (LCSH): | Logperch, Fishes -- Morphogenesis, Cell differentiation, DNA damage , Mutation (Biology), Epithelial cells | ||||||
| Journal or Publication Title: | eLife | ||||||
| Publisher: | eLife Sciences Publications, Ltd | ||||||
| ISSN: | 2050-084X | ||||||
| Official Date: | 30 May 2022 | ||||||
| Dates: |
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| Volume: | 11 | ||||||
| Page Range: | e72302 | ||||||
| DOI: | 10.7554/elife.72302 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||
| Date of first compliant deposit: | 24 November 2022 | ||||||
| Date of first compliant Open Access: | 25 November 2022 | ||||||
| RIOXX Funder/Project Grant: |
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