PUBLICATION
Genetic deletion of hspa8 leads to selective tissue malformations in zebrafish embryonic development
- Authors
- Wang, C., Zhang, X., Wang, X., Zhai, Y., Li, M., Pan, J., Bai, Y., Rong, X., Zhou, J.
- ID
- ZDB-PUB-221018-40
- Date
- 2022
- Source
- Journal of Cell Science 135(21): (Journal)
- Registered Authors
- Li, Mengjiao, Rong, Xiaozhi, Wang, Caixia, Zhou, Jianfeng
- Keywords
- ATF4, Hspa8/Hsc70, Pharyngeal arch cartilages, Unfolded protein response, Zebrafish, eIF2α
- MeSH Terms
-
- Animals
- Embryonic Development/genetics
- Endoplasmic Reticulum Stress/genetics
- Eukaryotic Initiation Factor-2*/metabolism
- Mice
- Mice, Knockout
- Unfolded Protein Response/genetics
- Zebrafish*
- PubMed
- 36226668 Full text @ J. Cell Sci.
Citation
Wang, C., Zhang, X., Wang, X., Zhai, Y., Li, M., Pan, J., Bai, Y., Rong, X., Zhou, J. (2022) Genetic deletion of hspa8 leads to selective tissue malformations in zebrafish embryonic development. Journal of Cell Science. 135(21):.
Abstract
The heat shock cognate 71 kDa protein HSPA8/HSC70, a constitutively expressed cognate member of the heat shock protein 70 family, plays an essential role in protein quality control and cell homeostasis maintenance. HSPA8 has been implicated in many diseases, including cancers and neurodegenerative diseases. Due to massive cell death after knockdown of HSPA8 and nonviable Hspa8 knockout mice, the physiological role of HSPA8 in vertebrates and its underlying mechanism have not yet been elucidated. To address this issue, we used CRISPR/Cas9 technology and genetically deleted hspa8 in zebrafish embryos. Genetic deletion of hspa8 resulted in malformations of the pharyngeal arches, pectoral fins, head, and eyes at the later stages. We next focused on pharyngeal arch deficiency and found that pharyngeal arches in hspa8 mutant embryos exhibited induction of endoplasmic reticulum stress and activation of the unfolded protein response via the Perk/p-eIF2α/Atf4 signaling cascade. Inhibition of Perk/p-eIF2α/Atf4 signaling rescued developmental deficiency of pharyngeal arches due to depletion of Hspa8. Taken together, our results provide novel insights into the tissue-specific roles of Hspa8 in the regulation of vertebrate embryonic development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping