Lee Hyung-Ok, Levorse John M, Shin Myung K
Cell and Developmental Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Dev Biol. 2003 Jul 1;259(1):162-75. doi: 10.1016/s0012-1606(03)00160-x.
Mutations in the genes encoding endothelin receptor-B (Ednrb) and its ligand endothelin-3 (Edn3) affect the development of two neural crest-derived cell types, melanocytes and enteric neurons. EDNRB signaling is exclusively required between E10.5 and E12.5 during the migratory phase of melanoblast and enteric neuroblast development. To determine the fate of Ednrb-expressing cells during this critical period, we generated a strain of mice with the bacterial beta-galactosidase (lacZ) gene inserted downstream of the endogenous Ednrb promoter. The expression of the lacZ gene was detected in melanoblasts and precursors of the enteric neuron system (ENS), as well as other neural crest cells and nonneural crest-derived lineages. By comparing Ednrb(lacZ)/+ and Ednrb(lacZ)/Ednrb(lacZ) embryos, we determined that the Ednrb pathway is not required for the initial specification and dispersal of melanoblasts and ENS precursors from the neural crest progenitors. Rather, the EDNRB-mediated signaling is required for the terminal migration of melanoblasts and ENS precursors, and this pathway is not required for the survival of the migratory cells.
编码内皮素受体B（Ednrb）及其配体内皮素-3（Edn3）的基因突变会影响两种神经嵴衍生细胞类型——黑素细胞和肠神经元的发育。在黑素母细胞和肠神经母细胞发育的迁移阶段，EDNRB信号传导仅在胚胎第10.5天至12.5天期间是必需的。为了确定在此关键时期表达Ednrb的细胞的命运，我们构建了一种小鼠品系，将细菌β-半乳糖苷酶（lacZ）基因插入到内源性Ednrb启动子的下游。在黑素母细胞和肠神经系统（ENS）的前体以及其他神经嵴细胞和非神经嵴衍生谱系中检测到了lacZ基因的表达。通过比较Ednrb(lacZ)/+和Ednrb(lacZ)/Ednrb(lacZ)胚胎，我们确定Ednrb信号通路对于黑素母细胞和ENS前体从神经嵴祖细胞的初始特化和分散不是必需的。相反，EDNRB介导的信号传导对于黑素母细胞和ENS前体的终末迁移是必需的，并且该信号通路对于迁移细胞的存活不是必需的。
