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 sub-types 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 fac-tor (GDNF) robustly stimulate neurite outgrowth from VSNs in vitro. Perinatally, BDNF was expressed by neu-rons 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 en-riched in VSN cell types that project to the gastrointestinal tract. Last, the 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, the 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.

Automated summary

Using VSN marker genes in adult mice, we investigated the developmental emergence and trophic factors regulating the growth of specialized vagal sub-types. BDNF and GDNF were found to stimulate neurite outgrowth from VSNs, with BDNF supporting VSNs locally and GDNF promoting growth in distal innervation sites in the gut. The expression patterns of many cell type markers in the nodose ganglion mature considerably by the end of the first postnatal week.