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

Neuron
Authors
Keywords
Abstract

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.

Year of Publication
2022
Journal
Neuron
Volume
110
Issue
14
Pages
2299-2314.e8
Date Published
2022 Jul 20
ISSN
1097-4199
DOI
10.1016/j.neuron.2022.04.026
PubMed ID
35613619
PubMed Central ID
PMC9308693
Links
Grant list
R01 DC005982 / DC / NIDCD NIH HHS / United States
R01 DK121409 / DK / NIDDK NIH HHS / United States