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

Qijing Xie, Jiefu Li, Hongjie Li, Namrata D. Udeshi, Tanya Svinkina, Daniel Orlin, Sayeh Kohani, Ricardo Guajardo, D. R. Mani, Chuanyun Xu, Tongchao Li, Shuo Han, Wei Wei, S. Andrew Shuster, David J. Luginbuhl, Stephen R. Quake, Swetha E. Murthy, Alice Y. Ting, Steven A. Carr, Liqun Luo

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2299-2314.e8
JournalNeuron
Volume110
Issue number14
DOIs
StatePublished - Jul 20 2022

Keywords

  • Drosophila
  • Piezo
  • antennal lobe
  • cell-surface protein
  • combinatorial code
  • dendrite targeting
  • olfactory circuit
  • proteome
  • transcription factor
  • wiring specificity

ASJC Scopus subject areas

  • Neuroscience(all)

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