CELLULAR-LOCALIZATION OF PAN-TRK IMMUNOREACTIVITY AND TRK(C) MESSENGER-RNA IN THE ENTERIC NERVOUS-SYSTEM

The members of the trk family of tyrosine receptor kinases, trk(A), tr k(B), and trk(C), are the functional receptors for neurotrophins, a fa mily of related neurotrophic factors. In this study, we investigated 1 ) the distribution of neurotrophin receptors in the developing and adu lt rat digestive tract with a pan-trk antibody that recognizes all kno wn trks and 2) the cellular localization of trk-encoding mRNAs in the adult gut with single-stranded RNA probes specific for trh(A), trk(B), and trk(C). In the developing myenteric plexus, trk. immunoreactivity was present at embryonic day (ED) 14. Cells and fibers immunoreactive for trk could be visualized in the myenteric plexus at ED 16. At this age, dense staining was found in thick bundles of fibers in proximity to the myenteric plexus in the longitudinal muscle and in association with blood vessels in the mesentery. At ED 18, trk immunoreactivity w as also seen in thin processes running from the myenteric plexus into the circular muscle, and in fibers and cells in intrapancreatic gangli a. By ED 20, immunoreactive staining was quite dense in both the myent eric and submucosal plexuses. At birth, virtually all enteric ganglia displayed strong trk immunoreactivity; the intensity of the staining a t this age made it difficult to discern individual cells. During postn atal development, there was a decrease in cell body staining and an in crease in the density of trk-containing fibers that became widely dist ributed to the gut wall and pancreas. The adult pattern of trk immunor eactivity was established between postnatal days 5 and 10. In adults, trk immunoreactivity was found in numerous enteric and intrapancreatic ganglion cells and in dense networks of fibers innervating all the la yers of the gut, the pancreas, and vasculature. The trk(C) mRNA was ex pressed in adult enteric ganglion cells of both the myenteric and subm ucous plexus. By contrast, the trk(A) and trk(B) mRNAs could not be de tected in enteric ganglia. Al three trk mRNAs were expressed in dorsal root ganglia, which were used as positive controls. The density and w ide distribution of trk immunoreactivity together with its persistence in adulthood support the concept that neurotrophins play a broad role in the digestive system from development through adult Life, perhaps being involved in differentiation, phenotypic expression, and tissue m aintenance. The presence of trk(C) mRNA in enteric neurons along with recent evidence that neurotrophin-3 plays a role in the development of the enteric nervous system suggest that trk(C) and neurotrophin-3 are a major neurotrophin system in the gastrointestinal tract. (C) 1996 W iley-Liss, Inc.