Ontogeny and Trophic Factor Sensitivity of Gastrointestinal Projecting Vagal Sensory Cell Types.

Vagal sensory neurons (VSNs) located in the nodose ganglion provide information, such as stomach stretch or the presence of ingested nutrients, to the caudal medulla via specialized cell types expressing unique marker genes. Here, we leverage VSN marker genes identified in adult mice to determine when specialized vagal subtypes arise developmentally and the trophic factors that shape their growth. Experiments to screen for trophic factor sensitivity revealed that brain derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) robustly stimulate neurite outgrowth from VSNs in vitro Perinatally, BDNF was expressed by neurons of the nodose ganglion itself, while GDNF was expressed by intestinal smooth muscle cells. Thus, BDNF may support VSNs locally, whereas GDNF may act as a target-derived trophic factor supporting the growth of processes at distal innervation sites in the gut. Consistent with this, expression of the GDNF receptor was enriched in VSN cell types that project to the gastrointestinal tract. Lastly, mapping of genetic markers in the nodose ganglion demonstrates that defined vagal cell types begin to emerge as early as embryonic day 13, even as VSNs continue to grow to reach gastrointestinal targets. Despite the early onset of expression for some marker genes, expression patterns of many cell type markers appear immature in prenatal life and mature considerably by the end of the first postnatal week. Together, the data support location-specific roles for BDNF and GDNF in stimulating VSN growth, and a prolonged perinatal timeline for VSN maturation in male and female mice. Significance Statement Subpopulations of gastrointestinal-projecting vagal sensory neurons (VSNs) in the nodose ganglia convey satiety signals from the gut to the brain that regulate feeding behavior. Here, we examine gene expression in developing VSNs to better understand how they mature in perinatal life as they are exposed to ingestive stimuli. We demonstrate that thousands of genes are differentially expressed in the nodose ganglia of early postnatal mice compared to adults, indicating that VSNs continue to mature well after consumption of the first meal. The data further highlight the postnatal maturation of specific VSN subtypes and their sensitivity to trophic factors that stimulate growth and innervation of the gastrointestinal tract.