The forkhead transcription factor FKH-7/FOXP acts in C. elegans chemosensory neurons to shape a life history strategy

Abstract Some organisms exhibit a remarkable ability to adapt their life history strategies within a single lifespan in response to dynamic biotic and abiotic cues, such as Caenorhabditis elegans larval facultative diapause. However, the molecular basis of how conspecific and prey cues are processed to conditionally alter the time to reproductive maturation remains largely unexplored. Here we discover that the longest transcript of the forkhead transcription factor FKH-7/FOXP is expressed and acts in C. elegans pheromone and bacteria-sensing neurons to promote larval development into growth-arrested diapause under resource-scarce conditions. We further demonstrate that human FOXP1 can functionally substitute for FKH-7 in these chemosensory neurons and that incorporating a hypomorphic missense mutation associated with a human neurodevelopmental disorder characterized by social interaction deficits reduces frequency of the adaptive response in nematode populations. In the fkh-7/FOXP1 missense variant, single-cell transcriptomics of chemosensory neurons identifies the set of candidate genes for deeper characterization of variant-specific molecular pathology at single neuron resolution in the context of an adaptive developmental decision.