The C. elegans uv1 neuroendocrine cells provide direct 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 C. 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 TRPV 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 cells 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. Significance Statement Neuroendocrine cells respond to diverse physical and chemical signals from the body, releasing hormones that control reproduction, gut motility, and fight or flight responses. Neuroendocrine cells are often found embedded in complex tissues, complicating studies of how they are activated. Using the genetic and experimental accessibility of C. elegans , we find the uv1 neuroendocrine cells of the egg-laying motor behavior circuit respond directly to mechanical stimulation and vulval opening. We show that L-type voltage-gated Ca2+ channels facilitate uv1 mechanical activation and also coordinate cell activation across the vulval opening. In contrast to other mechanically activated cells, uv1 activation does not require Piezo or TRPV channels. This work shows how neuroendocrine cells relay critical mechanosensory feedback to circuits that control reproduction. ### Competing Interest Statement The authors have declared no competing interest.