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Neuron DOI:10.1016/j.neuron.2022.04.026

Transcription factor Acj6 controls dendrite targeting via a combinatorial cell-surface code.

Publication TypeJournal Article
Year of Publication2022
AuthorsXie, Q, Li, J, Li, H, Udeshi, ND, Svinkina, T, Orlin, D, Kohani, S, Guajardo, R, Mani, DR, Xu, C, Li, T, Han, S, Wei, W, S Shuster, A, Luginbuhl, DJ, Quake, SR, Murthy, SE, Ting, AY, Carr, SA, Luo, L
Date Published2022 Jul 20
KeywordsAnimals, Dendrites, Drosophila, Drosophila Proteins, Ion Channels, Membrane Proteins, Nerve Tissue Proteins, Olfactory Pathways, Olfactory Receptor Neurons, POU Domain Factors, Proteomics, Transcription Factors

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. Combined 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.


Alternate JournalNeuron
PubMed ID35613619
PubMed Central IDPMC9308693
Grant ListR01 DC005982 / DC / NIDCD NIH HHS / United States
R01 DK121409 / DK / NIDDK NIH HHS / United States