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

In the developing Drosophila central nervous system (CNS), neural progenitor (neuroblast [NB]) selection is gated by lateral inhibition, controlled by Notch signaling and proneural genes. However, proneural mutants still generate many NBs, indicating the existence of additional proneural genes. Moreover, recent studies reveal involvement of key epithelial-mesenchymal transition (EMT) genes in NB selection, but the regulatory interplay between Notch signaling and the EMT machinery is unclear. We find that SoxNeuro (SoxB family) and worniu (Snail family) are integrated with the Notch pathway, and constitute the missing proneural genes. Notch signaling, the proneural, SoxNeuro, and worniu genes regulate key EMT genes to orchestrate the NB selection process. Hence, we uncover an expanded lateral inhibition network for NB selection and demonstrate its link to key players in the EMT machinery. The evolutionary conservation of the genes involved suggests that the Notch-SoxB-Snail-EMT network may control neural progenitor selection in many other systems.Funding Agencies|Swedish Research CouncilSwedish Research Council [621-2013-5258, 2017-04061]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [KAW2012.0101, KAW2017.0312]; Swedish Cancer Foundation [CAN2017/257]; University of QueenslandUniversity of Queensland