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Identifying molecular instructions to hard-wire a sensory neurons synaptic connectivity

dos Santos, J. V.; Yu, R. Y.; Terceros, A.; Pires, P. M.; Rusu, D.; Cvektkovska, V.; Bucio-Mendez, A.; Lin, T.-J.; Emran, F.; Djambazian, H.; Berube, P.; Sladek, R.; Chen, B. E.

2026-04-22 neuroscience
10.64898/2026.04.22.720075 bioRxiv
Show abstract

The neural circuitry underlying innate behaviours must be pre-specified using precise molecular instructions. However, it is not clear what specific molecules are required to generate one neurons wiring pattern that make it distinct from a neighboring neurons wiring pattern. Here, we repeatedly sequenced three identified Drosophila sensory neurons that each have a unique and stereotyped hard-wired synaptic connectivity, to determine the cell surface molecules that distinguish their identities. Repeated sequencing of the same neuron between different animals revealed that the variability of transcription is < 1%. We find that less than 100 cell surface molecules can distinguish between a mechanosensory neuron from a chemosensory neuron. Functional characterization of the cell surface receptors verified their different roles in axonal and synaptic targeting. Finally, we expressed combinations of the different cell surface receptors to mis-wire the chemosensory neuron and increase its axonal branching.

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