Genome-wide binding profiles of KDM5 in Drosophila GMCs and immature neurons

Mutations in the lysine demethylase 5 (KDM5) family of transcriptional regulators are associated with intellectual disability, yet little is known regarding the spatiotemporal requirements or neurodevelopmental contributions of KDM5 proteins. Utilizing the mushroom body (MB), a major learning and memory center within the Drosophila brain, we demonstrate that KDM5 is specifically required within ganglion mother cells and immature neurons for proper neurodevelopment. Within this cellular subpopulation, we identify a core network of KDM5-regulated and -bound genes that are critical modulators of neurodevelopment. Significantly, we find that a majority of these genes are direct targets of Prospero (Pros), a transcription factor with well-established roles in neurodevelopment in other neuronal contexts. We demonstrate that Pros is essential for MB development and show that KDM5 binds to pros and regulates its expression. We therefore provide evidence for a KDM5-Pros axis that orchestrates a transcriptional program critical for proper neurodevelopment. Overall design: 9 samples with 6 biological replicates for R71C09 > dam:kdm5 with tubulin-Gal80[ts] and 3 biological replicates for R71C09 > dam with tubulin-Gal80[ts].