Wexler, L. R. | bioRxiv Science

bioRxiv2026

A stereotyped glial attachment determines the morphology and function of neuronal cilia

Primary cilia are signaling hubs that influence nearly every aspect of cell physiology. Neuronal primary cilia were recently discovered to interact with glia in the mammalian brain, but how cilia-glia attachments form and what roles they play remain unknown. Here, we find that two C. elegans sensory neurons (URX and BAG) use their primary cilia to attach to a specific glial partner (ILsoL). Through a genetic screen, we find that cilia-glia attachment requires BUG-1, a secreted protein with conserved cell adhesion domains that localizes to the cilia-glia attachment site. In the absence of BUG-1, neuronal cilia are present but fail to attach to the glial cell. We find that loss of cilia-glia attachment alters cilia morphology and disrupts stimulus-evoked calcium dynamics in cilia. We propose that primary cilia not only act as antennae for long-range cell communication, but also form close-range cell attachments that modulate cell signaling.

developmental biology↗

bioRxiv2019

A neuroendocrine feedback loop in C. elegans males integrates food detection and biological sex to modulate chemoreceptor expression and behavioral flexibility

Dynamic integration of internal and external cues is essential for flexible, adaptive animal behavior. In C. elegans, biological sex and feeding state regulate expression of the food-associated chemoreceptor odr-10, contributing to plasticity in food detection and the decision between feeding and exploration. In adult hermaphrodites, odr-10 expression is high; in well-fed adult males, odr-10 expression is low, promoting exploratory mate-searching behavior. Food-deprivation transiently activates male odr-10 expression, heightening food sensitivity and reducing food-leaving. Here, we identify a neuroendocrine feedback loop that sex-specifically regulates odr-10 in response to food deprivation. In well-fed males, insulin-like (IIS) and TGF{beta} signaling repress odr-10 expression. Upon food deprivation, odr-10 is directly activated by DAF-16/FoxO, the canonical C. elegans IIS effector. The TGF{beta} ligand DAF-7 acts upstream of IIS, and, likely because of its sexually dimorphic expression in the nervous system, links feeding to odr-10 only in males. Surprisingly, these responses to food deprivation are not triggered by internal metabolic cues, but rather by the loss of sensory signals from food. In the presence of inedible food, males become metabolically starved but express levels of odr-10 and daf-7 comparable to those of well-fed males. Further, exposing food-deprived males to inedible food is sufficient to restore low odr-10 expression. Food signals are detected by a small number of sensory neurons whose activity non-autonomously regulates daf-7 expression, IIS, and odr-10. Thus, adult C. elegans males employ a neuroendocrine feedback loop that integrates food detection and genetic sex to dynamically modulate chemoreceptor expression and sensory behavior.

neuroscience↗