@article{66e6d9545d5e421ab67963309253a8f8,
title = "A kdm5–prospero transcriptional axis functions during early neurodevelopment to regulate mushroom body formation",
abstract = "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.",
author = "Hatch, {Hayden A.M.} and Belalcazar, {Helen M.} and Marshall, {Owen J.} and Julie Secombe",
note = "Funding Information: We thank all the frontline and essential workers who worked tirelessly to protect and assist others during the COVID-19 pandemic. We additionally thank Nicholas Baker, Hannes B{\"u}low, Andreas Jenny, Bernice Morrow, Anna Francesconi, and all members of the Secombe Lab for their feedback and edits on the manuscript. We appreciate the confocal microscope training and assistance provided to us by Hillary Guzik and members of the Einstein Analytical Imaging Facility (AIF). We thank Gilbert Henry and Andrea Brand for their generous donations of fly stocks and reagents. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were also used in this study. The 1D4 and 9.4A monoclonal antibodies were obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at the University of Iowa. We are additionally grateful to the NIH Special Instrument Grant S10OD023591 and the Cancer Center Support Grant P30CA013330. This research was supported by the NIH Ruth L Kirschstein National Research Service Award F31NS110278, the Einstein MSTP Training Grant T32GM007288, and the Junior Investigator in Neuroscience Research Award (JINRA) from the Dominick P Purpura Department of Neuroscience to HAMH, NIH R01GM112783 and support from the Irma T Hirschl Trust to JS, and NHMRC grants APP1128784 and APP1185220 to OJM. Publisher Copyright: {\textcopyright}Hatch et al.",
year = "2021",
month = mar,
doi = "10.7554/eLife.63886",
language = "English (US)",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}