PUBLICATION
Nrf2 dictates the neuronal survival and differentiation of embryonic zebrafish harboring compromised alanyl-tRNA synthetase
- Authors
- Jin, B., Xie, L., Zhan, D., Zhou, L., Feng, Z., He, J., Qin, J., Zhao, C., Luo, L., Li, L.
- ID
- ZDB-PUB-220806-10
- Date
- 2022
- Source
- Development (Cambridge, England) 149(17): (Journal)
- Registered Authors
- Li, Li, Luo, Lingfei, Zhao, CongJian
- Keywords
- Aars1, Neuronal apoptosis, Nrf2, PERK, UPR, Zebrafish
- Datasets
- GEO:GSE196846
- MeSH Terms
-
- Alanine-tRNA Ligase*
- Animals
- Cell Differentiation/genetics
- Cell Survival/genetics
- Mammals/metabolism
- NF-E2-Related Factor 2*/genetics
- NF-E2-Related Factor 2*/metabolism
- Zebrafish
- PubMed
- 35929539 Full text @ Development
Citation
Jin, B., Xie, L., Zhan, D., Zhou, L., Feng, Z., He, J., Qin, J., Zhao, C., Luo, L., Li, L. (2022) Nrf2 dictates the neuronal survival and differentiation of embryonic zebrafish harboring compromised alanyl-tRNA synthetase. Development (Cambridge, England). 149(17).
Abstract
tRNA synthetase deficiency leads to unfolded protein responses in neuronal disorders; however, its function in embryonic neurogenesis remains unclear. This study identified an aars1cq71/cq71 mutant zebrafish allele that showed increased neuronal apoptosis and compromised neurogenesis. aars1 transcripts were highly expressed in primary neural progenitor cells, and their aberration resulted in protein overloading and activated Perk. nfe2l2b, a novel paralog of mammalian Nrf2, is a pivotal executor of Perk signaling that regulates neuronal phenotypes in aars1cq71/cq71 mutants. Interference of nfe2l2b in nfe2l2b△1/△1 mutants did not affect global larval development. However, aars1cq71/cq71;nfe2l2b△1/△1 mutant embryos exhibited increased neuronal cell survival and neurogenesis compared to their aars1cq71/cq71 siblings. nfe2l2b was harnessed by Perk at two levels. Its transcript was regulated by Chop, an implementer of Perk. It was also phosphorylated by Perk. Both pathways synergistically assured the nuclear functions of nfe2l2b to control cell survival by targeting p53. Our study extends the understanding of tRNA synthetase in neurogenesis and implies that Nrf2 is a cue to mitigate neurodegenerative pathogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping