A Genetic Screen inDrosophilauncovers a role forsenseless-2in surface glia in the peripheral nervous system to regulate CNS morphology

Abstract

AbstractDespite increasing in mass approximately 100-fold during larval life, theDrosophilaCNS maintains its characteristic form during this rapid growth phase. Dynamic interactions between the overlying basement membrane and underlying surface glia are known to regulate CNS structure inDrosophila, but the genes and pathways that establish and maintain CNS morphology during development remain poorly characterized. To identify genes that regulate CNS shape inDrosophila, we conducted an EMS-based, forward genetic screen of the second chromosome, uncovered 50 mutations that disrupt CNS structure, and mapped these alleles to 17 genes. Whole genome sequencing revealed the affected gene for all but one mutation. Identified genes include well characterized regulators of tissue shape, likeLanB1, viking, and Collagen type IV alpha1, as well as previously characterized genes, such asToll-2andRme-8, with no known role in regulating CNS structure. We also uncovered thatpapilinandC1GalTAlikely act in the same pathway to regulate CNS structure and found that the fly homolog of a glucuronosyltransferase, B4GAT1/LARGE1, that regulates Dystroglycan function in mammals is required to maintain CNS shape inDrosophila. Finally, we show that thesenseless-2transcription factor is expressed and functions specifically in surface glia found on peripheral nerves but not those on the CNS proper to govern CNS structure, identifying a gene that functionally subdivides a glial subtype along the peripheral-central axis. Future work on these genes should clarify the genetic mechanisms that ensure the homeostasis of CNS shape and form during development.