Pancreatic organogenesis is a complex, multistep process whereby multiple cell types must migrate, proliferate, and differentiate in a strict spatiotemporal manner to ultimately form the complete organ. Although pancreatic epithelial organogenesis is well characterized, the peripheral nervous system (PNS) innervating the organ is poorly understood. Although the PNS has been shown to be critical in the formation of other budding exocrine organs, and therefore likely plays a role in the formation of the pancreas, there is a dearth of information on innervation of this developing organ. To this end, our lab has taken advantage of an explant culture system and single-cell RNA-sequencing (scRNAseq) to characterize the nerves supplying the developing pancreas. Imaging of whole pancreata reveals that peripheral nerves develop in parallel with the pancreas, with intrapancreatic ganglia being present from early stages. Using scRNAseq analysis we have begun to decipher the timing of pancreatic PNS progenitor cell differentiation, and the potential signaling pathways guiding axonal growth and morphogenesis. Continued investigation of the mechanisms guiding innervation of the pancreas, deciphering how nerve-epithelial interactions are established and defining signaling pathways activated by the nerves will allow us to discover the role of the PNS in pancreatic morphogenesis, as well as mis-regulation during disease.
S. de la O: None. L. Byrnes: None. D.M. Wong: None. S. Knox: None. J.B. Sneddon: Advisory Panel; Spouse/Partner; Akouos. Advisory Panel; Self; Encellin. Advisory Panel; Spouse/Partner; Encellin. Consultant; Self; Semma Therapeutics, Inc.