期刊
DEVELOPMENTAL CELL
卷 47, 期 1, 页码 38-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2018.09.013
关键词
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资金
- NICHD
- European Research Council (ERC)
- Women Health Research Center
- Chan Zuckerberg Initiative (CZI)
- HHMI International Scholar award
- European Research Council Consolidator Grant (ERC-COG) [724471-HemTree2.0]
- MRA Established Investigator Award [509044]
- Israel Science Foundation [703/15]
- Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine
- Helen and Martin Kimmel award for innovative investigation
- Minerva Stiftung research grant
- Israeli Ministry of Science, Technology, and Space
- David and Fela Shapell Family Foundation
- NeuroMac DFG/Transregional Collaborative Research Center Grant
- International Progressive MS Alliance/NMSS [PA-1604-08459]
- Adelis Foundation grant
Developmental neuronal remodeling is an evolutionarily conserved mechanism required for precise wiring of nervous systems. Despite its fundamental role in neurodevelopment and proposed contribution to various neuropsychiatric disorders, the underlying mechanisms are largely unknown. Here, we uncover the fine temporal transcriptional landscape of Drosophila mushroom body gamma neurons undergoing stereotypical remodeling. Our data reveal rapid and dramatic changes in the transcriptional landscape during development. Focusing on DNA binding proteins, we identify eleven that are required for remodeling. Furthermore, we sequence developing y neurons perturbed for three key transcription factors required for pruning. We describe a hierarchical network featuring positive and negative feedback loops. Superimposing the perturbation-seq on the developmental expression atlas highlights a framework of transcriptional modules that together drive remodeling. Overall, this study provides a broad and detailed molecular insight into the complex regulatory dynamics of developmental remodeling and thus offers a pipeline to dissect developmental processes via RNA profiling.
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