Evolutionarily conserved TM2D genes regulate Notch signaling and neuronal function in Drosophila

By generating the first clean knockout alleles of the fly genes that correspond to human TM2D1 (biscotti), TM2D2 (amaretto) and TM2D3 (almondex) genes, and further generating a triple knockout line, we found that this group of genes all regulate neurogenesis by regulating embryonic Notch signaling. We further identified that TM2D3, which is associated with late-onset Alzheimer's Disease, is also required for proper function and maintenance of the nervous system in adult flies.