The non-canonical thioreductase Tmx2b is essential for neuronal survival during zebrafish embryonic brain 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 b

SUBMITTER: Dekker J 

PROVIDER: S-EPMC12516324 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature