Sensory input, sex, and function shape hypothalamic cell type development

Mammalian behavior and physiology undergo dramatic changes in early life. Young animals rely on conspecifics to meet their needs and start displaying nutritional independence and sex-specific social interactions at weaning and puberty, respectively. How neuronal populations regulating homeostatic functions and social behaviors develop during these transitions remains unclear. We used paired transcriptomic and chromatin accessibility profiling to examine the developmental trajectories of neuronal populations in the hypothalamic preoptic region, where cell types with key roles in physiological and behavioral control have been identified1–6. These data reveal a remarkable diversity of developmental trajectories shaped by the sex of the animal, and the location and behavioral or physiological function of the corresponding cell types. We identify key stages of preoptic development, including early diversification, perinatal emergence of sex differences, postnatal maturation and refinement of signaling networks, and nonlinear transcriptional changes accelerating at the time of weaning and puberty. We assessed preoptic development in various sensory mutants and find a major role for vomeronasal sensing in the timing of preoptic cell type maturation. These results provide novel insights into the development of neurons controlling homeostatic functions and social behaviors and lay ground for examining the dynamics of these functions in early life. To build a transcriptional atlas of POA development, we performed droplet-based paired snRNA-seq and snATAC-seq at nine ages from E14 to P65, using the 10x Multiome kit, separately in males and females. We performed POA multiome sequencing on mutant and littermate control strains as well, focusing on mutants that affect specific sensory modalities, as well as dark-reared animals. In our initial submission to GEO, we are uploading only GEX (i.e. snRNA-seq) data; ATAC-seq data will follow.