Figure 1.

DNA methyltransferase 1 (DNMT1) promotes the survival of immature migrating inhibitory interneurons of the cerebral cortex.

DNMT1 seems to inhibit the expression of pro-apoptotic genes of the PAK family like Pak6 as well as genes encoding for MAP-kinases (MAPK) and BCL2 family members to ensure the proper survival and typical migratory phenotype of immature interneurons with leading and trailing process (DNMT1 wild type (WT)). Furthermore, Dnmt1 seems to repress transcription factors like FOXO1 with potential impact on cell death induction. Dnmt1 deletions abolish the repression of these pro-apoptotic genes resulting in increased expression in migrating interneurons during development (DNMT1 knockout (KO)). The subsequent activation of each other and downstream signaling pathways by phosphorylation events could facilitate morphological defects and results in increased mortality.