Expression of endothelin 3 by mesenchymal cells of embryonic mouse caecum

M A Leibl,^a T Ota,^d M N Woodward,^b S E Kenny,^b D A Lloyd,^b C R Vaillant,^c D H Edgar^a

^a Department of Human Anatomy and Cell Biology, The University of Liverpool, Ashton Street, Liverpool L69 3GE, UK, ^b Department of Child Health, The University of Liverpool, UK, ^c Department of Veterinary Preclinical Sciences, University of Liverpool, UK, ^d Department of Pathology, Kanazawa Medical University, Ishikawa, Japan

Correspondence to: Dr D H Edgar.

Accepted for publication 19 August 1998

BackgroundMutations in endothelin 3 (EDN3) and endothelin B receptor (EDNRB) genes cause terminal colonic aganglionosis in mice, and mutations in these genes have also been linked to the terminal aganglionosis seen in human Hirschsprung's disease. However, details of EDN3 expression during embryogenesis are lacking, and consequently the cellular mechanism by which EDN3 regulates innervation of the terminal gut is unclear.
AimsTo localise the expression of EDN3 and EDNRB in the embryonic mouse gut.
MethodsExpression of EDN3 and EDNRB mRNA was analysed by reverse transcription polymerase chain reaction and in situ hybridisation.
ResultsHigh 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 cell marker PGP9.5.
ConclusionsMesenchymal cells of the caecum express high levels of EDN3 mRNA during embryogenesis and hence the production of EDN3 at the caecum is likely to act on neural crest cells as a paracrine factor necessary for subsequent innervation of the terminal gut.
(GUT 1999;44:246-252)

Keywords: endothelin 3;  embryogenesis;  enteric nervous system;  neural crest cells;  gene expression