Leibl M A, Ota T, Woodward M N, Kenny S E, Lloyd D A, Vaillant C R, Edgar D H
Department of Human Anatomy and Cell Biology, The University of Liverpool, Ashton Street, Liverpool L69 3GE, UK.
Gut. 1999 Feb;44(2):246-52. doi: 10.1136/gut.44.2.246.
Mutations 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.
To localise the expression of EDN3 and EDNRB in the embryonic mouse gut.
Expression of EDN3 and EDNRB mRNA was analysed by reverse transcription polymerase chain reaction and in situ hybridisation.
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 cell marker PGP9.5.
Mesenchymal 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.
内皮素3（EDN3）和内皮素B受体（EDNRB）基因的突变会导致小鼠终末结肠神经节细胞缺失，这些基因的突变也与人类先天性巨结肠病中所见的终末神经节细胞缺失有关。然而，胚胎发育过程中EDN3表达的细节尚不清楚，因此EDN3调节终末肠道神经支配的细胞机制也不明确。
在胚胎期小鼠肠道中定位EDN3和EDNRB的表达。
通过逆转录聚合酶链反应和原位杂交分析EDN3和EDNRB mRNA的表达。
在神经嵴细胞到达之前和之后，EDN3 mRNA的高水平表达局限于盲肠的间充质细胞。相比之下，沿肠道的EDNRB表达呈现出与蛋白酪氨酸激酶ret和神经嵴细胞标志物PGP9.5相似的时间依赖性模式。
盲肠的间充质细胞在胚胎发育过程中表达高水平的EDN3 mRNA，因此盲肠中EDN3的产生可能作为旁分泌因子作用于神经嵴细胞，这是终末肠道后续神经支配所必需的。
