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Mutations in the lysine demethylase 5 (KDM5) family of transcriptional regulators are associated with intellectual disability, yet little is known regarding their spatiotemporal requirements or neurodevelopmental contributions. Utilizing the mushroom body (MB), a major learning and memory center within the Drosophila brain, we demonstrate that KDM5 is required within ganglion mother cells and immature neurons for proper axogenesis. Moreover, the mechanism by which KDM5 functions in this context is independent of its canonical histone demethylase activity. Using in vivo transcriptional and binding analyses, we identify a network of genes directly regulated by KDM5 that are critical modulators of neurodevelopment. We find that KDM5 directly regulates the expression of prospero, a transcription factor that we demonstrate is essential for MB morphogenesis. Prospero functions downstream of KDM5 and binds to approximately half of KDM5-regulated genes. Together, our data provide evidence for a KDM5– Prospero transcriptional axis that is essential for proper MB development.

Item Type:	Refereed Article
Keywords:	D. melanogaster, KDM5, Kenyon cell, chromosomes, gene expression, histone demethylase, intellectual disability, mushroom body, neuroscience, transcription factors
Research Division:	Biological Sciences
Research Group:	Genetics
Research Field:	Developmental genetics (incl. sex determination)
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Diagnosis of human diseases and conditions
UTAS Author:	Marshall, OJ (Dr Owen Marshall)
ID Code:	147346
Year Published:	2021
Web of Science® Times Cited:	7
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2021-10-27
Last Modified:	2022-08-19
Downloads:	6 View Download Statistics