* contributed equally
Complex behaviors are modulated by endocrine neurons, which secrete neuropeptides and hormones. Homeostasis of these neuromodulators is critical, and its disruption has been associated with disease. Despite the ancient and significant role that neuromodulators play in complex behaviors across organisms, a comprehensive understanding of neuroendocrine cell function and their regulation is limited.
The C. elegans nervous system provides an excellent genetic platform to investigate neural network functions and behavior. However, despite a fully annotated nervous system, a neuron with dedicated neurosecretory properties has not been identified. Using serial transmission electron microscopy, we identified RID as a potential endocrine cell. RID is the only neuron that extends an axon along the full length of the dorsal nerve cord and almost exclusively contains dense core vesicles, which package and secrete neuromodulators. Using a combination of laser ablation, genetics, and imaging techniques, we provide several lines of evidence that the RID neuron is a neuroendocrine cell that modulates motor behaviors. Using transcriptome profiling of a subpopulation of neurons isolated from both wild-type and unc-39 mutant worms, wherein the RID neuron is absent, we found that the RID neuron is enriched with neuropeptides, including flp-14. We confirm that flp-14 is expressed in the RID neuron and that flp-14 mutants possess locomotor defects similar to RID mutants. Our results demonstrate a neuromodulatory role for the RID neuron in regulating locomotion. We propose that the C. elegans RID neuron may be a useful genetic model to probe for conserved molecular mechanisms underlying neuroendocrine cell development and function. .
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