AbstractVagal sensory neurons located in the nodose ganglion provide a direct line of communication from gut to the brain. Information such as stomach stretch or the presence of ingested nutrients in the intestine is conveyed by specialized cell types that express unique marker genes. Here we leverage these vagal cell type marker genes identified in adults to further understand when specialized vagal subtypes arise developmentally and the factors that shape their growth and target innervation.

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... nitial sequencing and pathway analysis identified an enrichment of differentially expressed genes related to axon growth and guidance, synaptic strengthening, and expression changes downstream of brain derived neurotrophic factor (BDNF) in samples from early postnatal nodose ganglia. Subsequent experiments using cultured nodose ganglion explants revealed that both BDNF and GDNF robustly stimulate neurite outgrowth from early postnatal nodose ganglion explants. Through anatomical examination of whole body trophic factor expression, BDNF was shown to be expressed by neurons of the nodose ganglion itself, while GDNF was expressed by the muscular layers of the developing intestine. These data suggest that BDNF may act to support vagal neurons as a locally derived trophic factor, while GDNF is more likely to act as a target derived trophic factor supporting vagal afferent neuron growth at distal innervation sites in the gut. Consistent with a role as a target derived neurotrophic factor, expression of the GDNF receptor, Gfra1, was enriched in vagal afferent cell types that project to the gastrointestinal tract. Lastly, vagal cell type markers were used to demonstrate that vagal cell type specification begins to emerge as early as E13 even as sensory neurons continue to grow to reach gastrointestinal targets. Expression patterns of individual cell type markers appear largely immature in prenatal life and mature considerably by the end of the first postnatal week. Together the data support a role for GDNF in supporting vagal sensory innervation of gastrointestinal targets and establish a prolonged timeline for vagal sensory cell type maturation.