RRC ID 64504
著者 Hatch HAM, Belalcazar HM, Marshall OJ, Secombe J.
タイトル A KDM5-Prospero transcriptional axis functions during early neurodevelopment to regulate mushroom body formation.
ジャーナル Elife
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.
巻・号 10
公開日 2021-3-17
DOI 10.7554/eLife.63886
PII 63886
PMID 33729157
PMC PMC7997662
MeSH Animals Central Nervous System / growth & development Central Nervous System / metabolism Drosophila / genetics Drosophila / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Gene Expression Regulation, Developmental Histone Demethylases / genetics Histone Demethylases / metabolism* Larva / growth & development Larva / metabolism Mushroom Bodies / metabolism* Mutation Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Neurons / metabolism Nuclear Proteins / genetics Nuclear Proteins / metabolism* Transcription Factors / genetics Transcription Factors / metabolism*
IF 7.08
リソース情報
ショウジョウバエ DGRC#104754