Transcription Factor Acj6 Controls Dendrite Targeting via Combinatorial Cell-Surface Codes
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PROVIDER: PRJNA826896 | ENA |
REPOSITORIES: ENA
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Project description:Transcription factors specify the fate and connectivity of developing neurons. We investigate how a lineage-specific transcription factor, Acj6, controls the precise dendrite targeting of Drosophila olfactory projection neurons (PNs) by regulating the expression of cell-surface proteins. Quantitative cell-surface proteomic profiling of wild-type and acj6 mutant PNs in intact developing brains and a proteome-informed genetic screen identified PN surface proteins that execute Acj6-regulated wiring decisions. These include canonical cell adhesion molecules and proteins previously not associated with wiring, such as Piezo, whose mechanosensitive ion channel activity is dispensable for its function in PN dendrite targeting. Comprehensive genetic analyses revealed that Acj6 employs unique sets of cell-surface proteins in different PN types for dendrite targeting. Combinatorial expression of Acj6 wiring executors rescued acj6 mutant phenotypes with higher efficacy and breadth than expression of individual executors. Thus, Acj6 controls wiring specificity of different neuron types by specifying distinct combinatorial expression of cell-surface executors.
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Transcription factors specify the fate and connectivity of developing neurons. To understand how distal neurites execute commands from these nucleus-residing factors to specify their connectivity, we investigated how a lineage-specific transcription factor, Acj6, controls the precise dendrite targeting of Drosophila olfactory projection neurons (PNs). Quantitative cell-surface proteomic profiling of wild-type and acj6 mutant PNs in intact developing brains and a proteome-informed genetic screen identified PN surface proteins that execute Acj6-regulated wiring decisions. These include canonical cell adhesion molecules and molecules previously not associated with wiring, such as the mechanosensitive ion channel Piezo. Ion channel activity is dispensable for Piezo's function in PN dendrite targeting. Combinatorial expression of Acj6 executors more strongly rescued specific acj6 mutant phenotypes than expression of individual executors. Together, our findings reveal that a key transcription factor controls wiring specificity of different neuron types by regulating expression of unique combinations of cell-surface executors.
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