The Adhesion GPCR Flamingo-Like 1 (FMIL-1) Directs Synapse Formation in a Nociceptive Circuit
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…
Scientists have discovered that a gene called FMIL-1 directs the formation of nerve connections, or synapses, in a pain-sensing circuit in the worm species C. elegans. Nociceptive neurons, known as PVD neurons, establish synapses with two types of interneurons, PVC and AVA, which in turn trigger escape responses to harmful stimuli.
To uncover genes responsible for these connections, researchers employed fluorescent markers to visualize PVD synapses with PVC and AVA. This investigation led to the identification of the LIM homeodomain transcription factor MEC-3 and its target, FMIL-1, which plays a crucial role in guiding PVD's connections with both PVC and AVA.
FMIL-1 belongs to the adhesion class of G Protein-coupled receptors (aGPCRs), a protein family whose members are also linked to synapse formation in mammals. The researchers demonstrated that FMIL-1 operates early in PVD and can even induce the formation of extra synapses in another circuit, indicating that FMIL-1 promotes synaptogenesis.
This discovery introduces a novel experimental circuit within C. elegans for examining neuronal connections and provides evidence that FMIL-1/aGPCRs are instrumental in regulating synapse formation.
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