Expression of endothelin 3 by mesenchymal cells of embryonic mouse caecum

Background-Mutations in endothelin 3 (EDN3) and endothelin B receptor (EDNR B) genes cause terminal colonic aganglionosis in mice, and mutations in the se genes have also been linked to the terminal aganglionosis seen in human Hirschsprung's disease. However, details of EDN3 expression during embryoge nesis are lacking, and consequently the cellular mechanism by which EDN3 re gulates innervation of the terminal gut is unclear. Aims-To localise the expression of EDN3 and EDNRB in the embryonic mouse gu t. Methods-Expression of EDN3 and EDNRB mRNA was analysed by reverse transcrip tion polymerase chain reaction and in situ hybridisation. Results-High levels of EDN3 mRNA expression were restricted to mesenchymal cells of the caecum before and after the arrival of neural crest cells. In contrast, EDNRB expression along the gut displayed a time dependent pattern similar to those of the protein tyrosine kinase ret and the neural crest c ell marker PGP9.5. Conclusions-Mesenchymal cells of the caecum express high levels of EDN3 mRN A during embryogenesis and hence the production of EDN3 at the caecum is li kely to act on neural crest cells as a paracrine factor necessary for subse quent innervation of the terminal gut.