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| Status |
Public on Dec 14, 2021 |
| Title |
A global timing mechanism regulates cell-type specific wiring programs |
| Organism |
Drosophila melanogaster |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
The assembly of neural circuits is dependent upon precise spatiotemporal expression of cell recognition molecules1–6. Factors controlling cell-type specificity have been identified7–9, but how timing is determined remains unknown. Here we describe the induction of a cascade of transcription factors by a steroid hormone (Ecdysone) in all fly visual system neurons spanning target recognition and synaptogenesis. We demonstrate through single cell sequencing that the Ecdysone pathway regulates the expression of a common set of targets required for synaptic maturation and cell-type specific targets enriched for cell surface proteins regulating wiring specificity. Transcription factors in the cascade regulate the expression of the same wiring genes in complex ways, including activation in one cell-type and repression in another. We show that disruption of the Ecdysone-pathway generates specific defects in dendritic and axonal processes and synaptic connectivity, with the order of transcription factor expression correlating with sequential steps in wiring. We also identify shared targets of a cell-type specific transcription factor and the Ecdysone pathway which regulate specificity. We propose neurons integrate a global temporal transcriptional module with cell-type specific transcription factors to generate different cell-type specific patterns of cell recognition molecules regulating wiring.
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| Overall design |
Single cell RNA-seq for 5 developing lamina neurons (L1-L5) in Drosophila visual system with different genetic perturbations (EcRDN, EcR RNAi, and Hr3 RNAi) at multiple time points (24hAPF, 48hAPF, 72hAPF and adult). Bulk RNA-seq and bulk ATAC seq for wild type developing L1 neurons.
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| Contributor(s) |
Jain S, Lin Y, Kurmangaliyev YZ, Zipursky SL |
| Citation(s) |
35197627 |
| |
| Submission date |
Dec 11, 2021 |
| Last update date |
Mar 17, 2022 |
| Contact name |
Ying Lin |
| Organization name |
University of California, Los Angeles
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| Street address |
675 Charles E. Young Drive South
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| City |
Los Angeles |
| State/province |
California |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (2) |
| GPL19132 |
Illumina NextSeq 500 (Drosophila melanogaster) |
| GPL21306 |
Illumina HiSeq 4000 (Drosophila melanogaster) |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA788151 |
| SRA |
SRP350367 |
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