The roles of TGFβ and serotonin signaling in regulation of germline progenitors in adult C. elegans hermaphrodites revealed by the effects of a male pheromone.

Abstract

Some developmental processes initiated in embryos or larvae persist into adulthood, a prominent example being maintenance of stem cells. To what extent are the mechanisms regulating these cell populations similar during different stages of life history? We have been studying how adult C. elegans hermaphrodites regulate the population of germline progenitor cells in response to the male pheromone ascr#10. Here we show that upon encountering ascr#10 adult hermaphrodites increase this cell population using mechanisms that are similar to but distinct from those previously revealed to be involved in the expansion of the germline in larvae. The core of the signaling axis in adults, as in larvae, consists of a neuronally-expressed TGFβ ligand DAF-7 and Notch-like LAG-2 signaling from the germline stem cell niche. An adult-specific serotonin signal acts upstream of DAF-7 to increase the population of germline progenitors, but only in actively egg-laying worms. Our results also suggest that during normal aging, declining expression of lag-2 and daf-7 contribute to germline senescence. Expression of these genes in aging hermaphrodites could be restored to youthful levels by ascr#10 or by pharmacological increase of serotonin signaling. We posit that neuronal signals regulate an environmentally appropriate rate of germline production in adults and argue that one driver of reproductive aging is the reduced expression of neuronal factors that regulate the germline.