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
  • Cell Differentiation/genetics
  • Zebrafish
  • Animals
  • Cell Survival/genetics
  • NF-E2-Related Factor 2*/genetics
  • NF-E2-Related Factor 2*/metabolism
  • Mammals/metabolism
  • Alanine-tRNA Ligase*
(all 8)
PubMed
35929539 Full text @ Development
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
Figures
No images available
Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cq16
    		Point Mutation
    jf4TgTransgenic Insertion
      zf3767
        		Small Deletion
        zf3768
          		Point Mutation
          zf3769
            		Small Deletion
            zf3770TgTransgenic Insertion
              zf3771TgTransgenic Insertion
                zf3772TgTransgenic Insertion
                  1 - 8 of 8
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                  Human Disease / Model
                  Sequence Targeting Reagents
                  Fish
                  Antibodies
                  Orthology
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  CeruleanEFGCerulean
                  Dendra2EFGDendra2
                  GCaMPEFGGCaMP
                  NTREFGNTR
                  1 - 4 of 4
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                  Mapping
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                  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).