The C. elegans uv1 Neuroendocrine Cells Provide Mechanosensory Feedback of Vulval Opening

Neuroendocrine cells react to physical, chemical, and synaptic signals originating from tissues and the nervous system, releasing hormones that regulate various body functions beyond the synapse. Neuroendocrine cells are often embedded in complex tissues making direct tests of their activation mechanisms and signaling effects difficult to study. In the nematode worm Caenorhabditis elegans, four uterine-vulval (uv1) neuroendocrine cells sit above the vulval canal next to the egg-laying circuit, releasing tyramine and neuropeptides that feedback to inhibit egg laying. We have previously shown uv1 cells are mechanically deformed during egg laying, driving uv1 Ca²⁺ transients. However, whether egg-laying circuit activity, vulval opening, and/or egg release triggered uv1 Ca²⁺ activity was unclear. Here, we show uv1 responds directly to mechanical activation. Optogenetic vulval muscle stimulation triggers uv1 Ca²⁺ activity following muscle contraction even in sterile animals. Direct mechanical prodding with a glass probe placed against the worm cuticle triggers robust uv1 Ca²⁺ activity similar to that seen during egg laying. Direct mechanical activation of uv1 cells does not require other cells in the egg-laying circuit, synaptic or peptidergic neurotransmission, or transient receptor potential vanilloid and Piezo channels. EGL-19 L-type Ca²⁺ channels, but not P/Q/N-type or ryanodine receptor Ca²⁺ channels, promote uv1 Ca²⁺ activity following mechanical activation. L-type channels also facilitate the coordinated activation of uv1 cells across the vulva, suggesting mechanical stimulation of one uv1 cell cross-activates the other. Our findings show how neuroendocrine cells like uv1 report on the mechanics of tissue deformation and muscle contraction, facilitating feedback to local circuits to coordinate behavior.