| RRC ID |
87478
|
| 著者 |
Dekker J, Lam W, van der Linde HC, Ophorst F, de Konink C, Schot R, Kremers GJ, Sanderson LE, Berdowski WM, van Woerden GM, Mancini GMS, van Ham TJ.
|
| タイトル |
The non-canonical thioreductase Tmx2b is essential for neuronal survival during zebrafish embryonic brain development.
|
| ジャーナル |
Development
|
| Abstract |
Biallelic variants in thioredoxin-related transmembrane 2 protein (TMX2) can cause a malformation of brain cortical development characterized by microcephaly, polymicrogyria and pachygyria by an unknown mechanism. To investigate and visualize how TMX2 loss disrupts brain development in vivo, we generated zebrafish deficient for TMX2 ortholog tmx2b, which during the first two developmental days showed normal brain developmental hallmarks. From 3 days onwards, however, tmx2b mutants had no locomotor activity; this was accompanied by cell death in the brain, but not in other organs or in the spinal cord. Strikingly, cell death in tmx2b mutants occurred specifically in post-mitotic neurons within a ∼1.5-h timeframe, whereas neuronal progenitor and radial glial cells were preserved, and could be suppressed by inhibiting neuronal activity. In vivo calcium imaging showed a persistent ∼2-fold increase in calcium in neurons after the onset of cell death. This suggests that calcium homeostasis underlies the tmx2b mutant brain phenotype. Our results indicate that TMX2 is an evolutionarily conserved, protective regulator essential specifically for post-mitotic neurons after their differentiation in the vertebrate embryonic brain.
|
| 巻・号 |
152(18)
|
| 公開日 |
2025-9-15
|
| DOI |
10.1242/dev.204348
|
| PII |
369038
|
| PMID |
40891441
|
| PMC |
PMC12516324
|
| MeSH |
Animals
Brain* / cytology
Brain* / embryology
Brain* / metabolism
Calcium / metabolism
Cell Death
Cell Differentiation
Cell Survival / genetics
Embryo, Nonmammalian
Gene Expression Regulation, Developmental
Mutation / genetics
Neurogenesis
Neurons* / cytology
Neurons* / metabolism
Zebrafish* / embryology
Zebrafish* / genetics
Zebrafish* / metabolism
Zebrafish Proteins* / genetics
Zebrafish Proteins* / metabolism
|
| IF |
5.611
|
| リソース情報 |
| ゼブラフィッシュ |
Tg(vglut2a:loxP-DsRed-loxP-GFP)
Tg(gad1b:GFP) |
