1. Chromosomes and Gene Expression
  2. Neuroscience
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A KDM5-Prospero transcriptional axis functions during early neurodevelopment to regulate mushroom body formation

  1. Hayden AM Hatch
  2. Helen M Belalcazar
  3. Owen J Marshall
  4. Julie Secombe  Is a corresponding author
  1. Albert Einstein College of Medicine, United States
  2. University of Tasmania, Australia
Research Article
  • Cited 1
  • Views 740
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Cite this article as: eLife 2021;10:e63886 doi: 10.7554/eLife.63886

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.

Data availability

TaDa data have been deposited in GEO under the accession codes GSE156101 and GSE166116.

The following previously published data sets were used

Article and author information

Author details

  1. Hayden AM Hatch

    Neuroscience, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Helen M Belalcazar

    Genetics, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Owen J Marshall

    Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Julie Secombe

    Genetics and Neuroscience, Albert Einstein College of Medicine, New York, United States
    For correspondence
    julie.secombe@einsteinmed.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5826-7547

Funding

National Institutes of Health (R01GM112783)

  • Julie Secombe

National Health and Medical Research Council (APP1128784)

  • Owen J Marshall

National Health and Medical Research Council (APP1185220)

  • Owen J Marshall

National Institutes of Health (F31NS110278)

  • Hayden AM Hatch

National Institutes of Health (T32GM007288)

  • Hayden AM Hatch

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Laura A Bradfield, University of Technology Sydney, Australia

Publication history

  1. Received: October 9, 2020
  2. Accepted: March 16, 2021
  3. Accepted Manuscript published: March 17, 2021 (version 1)
  4. Version of Record published: March 26, 2021 (version 2)

Copyright

© 2021, Hatch et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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