Innervation of the mammalian pancreas is crucial for endocrine and exocrine function. Neural crest cells that give rise to neural progenitor cells are responsible for intrinsic pancreatic innervation, but the specific cues that guide this process in the developing embryo are largely unknown. Now, on , David Cano and colleagues identify glial cell line-derived neurotrophic factor (GDNF) as a key player in this process. They show that GDNF is expressed in the developing pancreatic epithelium and that conditional GDNF inactivation results in a marked reduction of neuronal and glial cells in both newborn and juvenile mice. In juveniles, parasympathetic innervation density decreased by just over half and appeared to be selectively reduced in pancreatic islets. Using wild-type E11.5 pancreatic explants, the authors demonstrate that GDNF can induce neural progenitor expansion and functions to promote the migration and differentiation of these progenitors. These results present a previously unappreciated role for GDNF in the regulation of neural crest-derived neural progenitor cells and the subsequent intrinsic innervation of the developing pancreas.
