Drosophila Neuroblast Selection Gated by Notch, Snail, SoxB and EMT Gene Interplay

SUMMARYIn the developing Drosophila central nervous system neural progenitor (neuroblast; NB) selection is gated by lateral inhibition, controlled by Notch signalling and proneural genes. However, proneural mutants only display partial NB reduction, indicating the existence of additional genes with proneural activity. In addition, recent studies reveal involvement of key epithelial-mesenchymal transition (EMT) genes in NB selection, but the regulatory interplay between Notch signalling and the EMT machinery is unclear. We find that the SoxB gene SoxNeuro and the Snail gene worniou are integrated with the Notch pathway, and constitute the missing proneural genes. Notch signalling, the proneural, SoxNeuro, and worniou genes regulate key EMT genes to orchestrate the NB specification process. Hence, we uncover an expanded lateral inhibition network for NB specification, and demonstrate its link to key players in the EMT machinery. Because of the evolutionary conservation of the genes involved, the Notch-SoxB-Snail-EMT network may control neural progenitor selection in many other systems.