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


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Hatch, HAM, Belalcazar, HM, Marshall, OJ ORCID: 0000-0003-1605-3871 and Secombe, J 2021 , 'A KDM5-Prospero transcriptional axis functions during early neurodevelopment to regulate mushroom body formation' , Elife, vol. 10 , pp. 1-29 , doi: 10.7554/eLife.63886.

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Mutations in the lysine demethylase 5 (KDM5) family of transcriptional regulators areassociated with intellectual disability, yet little is known regarding their spatiotemporalrequirements or neurodevelopmental contributions. Utilizing the mushroom body (MB), a majorlearning and memory center within the Drosophila brain, we demonstrate that KDM5 is requiredwithin ganglion mother cells and immature neurons for proper axogenesis. Moreover, themechanism by which KDM5 functions in this context is independent of its canonical histonedemethylase activity. Using in vivo transcriptional and binding analyses, we identify a network ofgenes directly regulated by KDM5 that are critical modulators of neurodevelopment. We find thatKDM5 directly regulates the expression of prospero, a transcription factor that we demonstrate isessential for MB morphogenesis. Prospero functions downstream of KDM5 and binds toapproximately 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: Article
Authors/Creators:Hatch, HAM and Belalcazar, HM and Marshall, OJ and Secombe, J
Keywords: D. melanogaster, KDM5, Kenyon cell, chromosomes, gene expression, histone demethylase, intellectual disability, mushroom body, neuroscience, transcription factors
Journal or Publication Title: Elife
Publisher: eLife Sciences Publications, Ltd.
ISSN: 2050-084X
DOI / ID Number: 10.7554/eLife.63886
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Copyright Hatch et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

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