A KDM5-Prospero transcriptional axis functions during early neurodevelopment to regulate mushroom body formation

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 wit...

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Bibliographic Details
Published in:	eLife Vol. 10
Main Authors:	Hatch, Hayden AM, Belalcazar, Helen M, Marshall, Owen J, Secombe, Julie
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 17-03-2021 eLife Sciences Publications Ltd eLife Sciences Publications, Ltd
Subjects:	Adults Analysis Animal cognition Animals Central Nervous System - growth & development Central Nervous System - metabolism Chromosomes and Gene Expression Drosophila Drosophila - genetics Drosophila - metabolism Drosophila melanogaster - genetics Drosophila melanogaster - metabolism Drosophila Proteins - genetics Drosophila Proteins - metabolism Gene expression Gene Expression Regulation, Developmental Genes Genetic aspects Genetic research Genetic transcription histone demethylase Histone Demethylases - genetics Histone Demethylases - metabolism Histones Insects Intellectual disabilities intellectual disability KDM5 Kenyon cell Larva - growth & development Larva - metabolism Lysine Morphogenesis Morphology Mushroom bodies Mushroom Bodies - metabolism mushroom body Mutation Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neurodevelopment Neuromodulation Neurons Neurons - metabolism Neuroscience Nuclear Proteins - genetics Nuclear Proteins - metabolism Proteins transcription factors Transcription Factors - genetics Transcription Factors - metabolism KDM5 Kenyon cell transcription factors neuroscience chromosomes mushroom body D. melanogaster histone demethylase gene expression intellectual disability
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Summary:	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 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 , 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.63886