| First Author | Wu JJ | Year | 1999 |
| Journal | Development | Volume | 126 |
| Issue | 6 | Pages | 1161-73 |
| PubMed ID | 10021336 | Mgi Jnum | J:52794 |
| Mgi Id | MGI:1330409 | Doi | 10.1242/dev.126.6.1161 |
| Citation | Wu JJ, et al. (1999) Inhibition of in vitro enteric neuronal development by endothelin-3: mediation by endothelin B receptors. Development 126(6):1161-73 |
| abstractText | The terminal colon is aganglionic in mice lacking endothelin-3 or its receptor, endothelin B. To analyze the effects of endothelin- 3/endothelin B on the differentiation of enteric neurons, E11-13 mouse gut was dissociated, and positive and negative immunoselection with antibodies to p75(NTR )were used to isolate neural crest- and non-crest- derived cells. mRNA encoding endothelin B was present in both the crest- and non-crest-derived cells, but that encoding preproendothelin-3 was detected only in the non-crest-derived population. The crest- and non- crest-derived cells were exposed in vitro to endothelin-3, IRL 1620 (an endothelin B agonist), and/or BQ 788 (an endothelin B antagonist). Neurons and glia developed only in cultures of crest-derived cells, and did so even when endothelin-3 was absent and BQ 788 was present. Endothelin-3 inhibited neuronal development, an effect that was mimicked by IRL 1620 and blocked by BQ 788. Endothelin-3 failed to stimulate the incorporation of [3H]thymidine or bromodeoxyuridine. Smooth muscle development in non-crest-derived cell cultures was promoted by endothelin-3 and inhibited by BQ 788. In contrast, transcription of laminin alpha1, a smooth muscle-derived promoter of neuronal development, was inhibited by endothelin-3, but promoted by BQ 788. Neurons did not develop in explants of the terminal bowel of E12 ls/ls (endothelin-3-deficient) mice, but could be induced to do so by endothelin-3 if a source of neural precursors was present. We suggest that endothelin-3/endothelin B normally prevents the premature differentiation of crest-derived precursors migrating to and within the fetal bowel, enabling the precursor population to persist long enough to finish colonizing the bowel. |
