A Genetic Screen for regulators of CNS morphology in Drosophila

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Despite increasing in mass approximately 100-fold during larval life, the Drosophila CNS 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 in Drosophila , but the genes and pathways that establish and maintain CNS morphology during development remain poorly characterized. To identify genes that regulate CNS shape in Drosophila , 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 gene. Identified genes include well characterized regulators of tissue shape, like Laminin B1, viking, and Collagen 4a1 , as well as characterized genes, such as Toll-2 and Rme-8 , with no known role in regulating CNS structure. We also uncovered that papilin and dC1GalTA likely act in the same pathway to regulate CNS structure and found that a glucuronosyltransferase that regulates Dystroglycan function in mammals is required to maintain CNS shape in Drosophila . Finally, we show that the senseless-2 transcription 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 the first gene that functionally subdivides a glial subtype along the peripheral-central axis. Future work on these genes should help clarify the genetic mechanisms that ensure the homeostasis of CNS shape and form during development.

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