The Function of the Endothelin Family in Neural Crest Development: An In Vitro S

小鼠突变致死斑点（ls）编码血管活性肽内皮素3（EDN 3），花斑（s）基因座编码其受体内皮素受体B（EDNRB）。这些基因中任一个突变的纯合子小鼠表现出无神经节巨克隆和白色斑点状被毛，这是由于结肠和皮肤的受影响部分缺乏神经嵴衍生的肠神经节和黑素细胞。为了了解这些基因在黑素细胞发育中的作用，我们使用原位杂交来确定这些基因相对于突变和正常胚胎中其他神经嵴标记物表达的时间。我们已经表明，这两个基因在小鼠胚胎发育过程中的神经嵴衍生细胞和表达模式发生变化，在各种神经嵴突变体的早期表达。我们已经确定，在我们开发的体外系统中，外源性添加的EDN3改变促进黑素细胞的增殖和分化。我们已经发现EDN3可以在该系统中成功地取代TPA，并导致黑素细胞增加50倍。我们发现，在EDN家族的相关成员（EDN 1和EDN 2）中，只有EDN 1可以替代EDN 3。我们还通过使用化学抑制剂表明，EDN 3的作用依赖于其受体EDNRB在神经嵴细胞上的存在。- 生物技术研究，癌症研究，消化系统疾病，基因图谱（非人类），神经科学，儿科研究，

The mouse mutant lethal spotting (ls) encodes the vasoactive peptide endothelin 3 (EDN3) and the piebald (s) locus encodes its receptor, endothelin receptor B (EDNRB). Mice homozygous for mutations in either of these genes exhibit aganglionic megaclon and a white spotted coat due to the lack of neural-crest derived enteric ganglia and melanocytes in affected portions of the colon and skin. In order to understand the role of these genes in melanocyte development, we are using in situ hybridization to determine the time that these genes are expressed relative to other neural crest markers in mutant and normal embryos. We have shown that both genes are expressed very early during mouse embryonic development in neural crest derived cells and expression patterns are altered in various neural crest mutants. We have determined that exogenously added EDN3 alters promotes proliferation and differentiation of melanocytes in an in vitro system that we have developed. We have found that EDN3 can successfully replace TPA in this system and results in a 50 fold increase in melanocytes. We have found that of the related family members (EDN1 and EDN2) only EDN1can substitute for EDN3 in this assay. We have also shown that the effect of EDN3 is dependent upon the presence of its receptor EDNRB on neural crest cells by using chemical inhibitors. - biotechnology research, cancer research, digestive diseases, gene mapping(non-human), neuroscience, pediatric research,