The Adhesion GPCR Flamingo-Like 1 (FMIL-1) Directs Synapse Formation in a Nociceptive Circuit
- 1University of California, Berkeley
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.
Related
- Trans-synaptic interaction of orphan GPCR GPR88 and adhesion GPCR BAI3 through C1ql1 maintains synapse integrity
- Clustering of the Adhesion-GPCR Latrophilin-3 Drives Excitatory Synapse Assembly
- Dynamic micropatterning uncovers spatial dynamics of B cell immune synapse formation
- Synaptic adhesion molecule signaling is activated and organized by tyrosine phosphorylation-induced biomolecular condensate formation
- Apical adhesion of meningococci controls host cell basal traction force through Ancreopodia formation
BibTeX
@misc{kennedy2026adhesion,
title = {{The Adhesion GPCR Flamingo-Like 1 (FMIL-1) Directs Synapse Formation in a Nociceptive Circuit}},
author = {T. Kennedy and D. Oje and K. Howerter and S. Reese and R. McWhirter and B. M. J. O'Brien and J. Stern and M. Ottley and D. Arac and E. Ozkan and R. Sando and A. Dillin and D. M. Miller},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748526},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748526v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - The Adhesion GPCR Flamingo-Like 1 (FMIL-1) Directs Synapse Formation in a Nociceptive Circuit
AU - T. Kennedy
AU - D. Oje
AU - K. Howerter
AU - S. Reese
AU - R. McWhirter
AU - B. M. J. O'Brien
AU - J. Stern
AU - M. Ottley
AU - D. Arac
AU - E. Ozkan
AU - R. Sando
AU - A. Dillin
AU - D. M. Miller
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748526
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748526v1
AB - 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.
ER -