A Neuroendocrine Modulation to Sustain C. elegans Forward Locomotion

Neuromodulators shape neural circuit dynamics. Combining electron microscopy, genetics, transcriptome profiling, calcium imaging and optogenetics, we discovered a peptidergic neuron that sustains C. elegans forward movement. The Six/SO-family homeobox transcription factor UNC-39 governs lineage-specific neurogenesis to give rise to a neuron called RID. RID bears hallmarks of a specialized neuroendocrine: it harbors near-exclusive dense core vesicle clusters along the axon, and expresses multiple neuropeptides, including FLP-14. RID activity increases during forward movement. Ablating RID reduces the sustainability of forward movement, a phenotype partially recapitulated by removing FLP-14. Activating RID prolongs forward movement, an effect that requires FLP-14. In summary, RID is a specialized endocrine neuron that promotes C. elegans forward motor state in part through a neuropeptide FLP-14.