PUBLICATION
DNA-damage induced cell death in yap1;wwtr1 mutant epidermal basal cells
- Authors
- Lai, J.K.H., Toh, P.J.Y., Cognart, H.A., Chouhan, G., Saunders, T.E.
- ID
- ZDB-PUB-220601-4
- Date
- 2022
- Source
- eLIFE 11: (Journal)
- Registered Authors
- Lai, Jason, Saunders, Timothy Edward
- Keywords
- cell biology, developmental biology, human, zebrafish
- MeSH Terms
-
- Animals
- Cell Death
- DNA/metabolism
- DNA Damage
- Epidermal Cells/metabolism
- Trans-Activators/metabolism
- YAP-Signaling Proteins
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 35635436 Full text @ Elife
Citation
Lai, J.K.H., Toh, P.J.Y., Cognart, H.A., Chouhan, G., Saunders, T.E. (2022) DNA-damage induced cell death in yap1;wwtr1 mutant epidermal basal cells. eLIFE. 11:.
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, D., 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping