The Adhesion GPCR Flamingo-Like 1 (FMIL-1) Directs Synapse Formation in a Nociceptive Circuit

Authors

Kennedy, T., Oje, D., Howerter, K., Reese, S., McWhirter, R., O'Brien, B. M. J., Stern, J., Ottley, M., Arac, D., Ozkan, E., Sando, R., Dillin, A., Miller, D. M.

Abstract

The species-specific anatomy of nervous systems suggests that circuit architecture is largely encoded by genetic blueprints. In C. elegans, PVD nociceptive neurons synapse with PVC and AVA interneurons to drive escape responses to noxious stimuli. We used fluorescent markers for PVD synapses with PVC and AVA in a candidate screen to detect connectivity genes. This approach revealed that the LIM homeodomain transcription factor MEC-3 and its target, FMIL-1 (Flamingo-like), function in PVD to direct connectivity with PVC and AVA. FMIL-1 is an adhesion class G Protein-coupled receptor (aGPCR), a protein family with members also implicated in mammalian synapse formation. We show that FMIL-1 acts early in PVD and is also sufficient to induce ectopic synapses in another circuit, thus suggesting that FMIL-1 promotes synaptogenesis. Our work establishes a new experimental circuit in C. elegans for investigating neuronal connectivity and provides evidence that FMIL-1/aGPCRs regulate synapse formation.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 07 Sep 2026.

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