Nataf V, Lecoin L, Eichmann A, Le Douarin N M
Institut d'Embryologie Cellulaire et Moléculaire du Centre National de la Recherche Scientifique, Nogent-sur-Marne, France.
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9645-50. doi: 10.1073/pnas.93.18.9645.
Disruptions of the genes encoding endothelin 3 (EDN3) and its receptor endothelin-B receptor (EDNRB) in the mouse result in defects of two neural crest (NC)-derived lineages, the melanocytes, and the enteric nervous system. To assess the mechanisms through which the EDN3/EDNRB signaling pathway can selectively act on these NC derivatives, we have studied the spatiotemporal expression pattern of the EDNRB gene in the avian embryo, a model in which NC development has been extensively studied. For this purpose, we have cloned the quail homologue of the mammalian EDNRB cDNA. EDNRB transcripts are present in NC cells before and during their emigration from the neural tube at all levels of the neuraxis. At later developmental stages, the receptor remains abundantly expressed in the peripheral nervous system including the enteric nervous system. In a previous study, we have shown that EDN3 enhances dramatically the proliferation of NC cells when they are at the pluripotent stage. We propose that the selective effect of EDN3 or EDNRB gene inactivation is due to the fact that both melanocytes and enteric nervous system precursors have to colonize large embryonic areas (skin and bowel) from a relatively small population of precursors that have to expand considerably in number. It is therefore understandable that a deficit in one of the growth-promoting pathways of NC cells has more deleterious effects on long-range migrating cells than on the NC derivatives which develop close to the neural primordium like the sensory and sympathetic ganglia.
在小鼠中，编码内皮素3（EDN3）及其受体内皮素B受体（EDNRB）的基因发生破坏会导致两种神经嵴（NC）衍生谱系出现缺陷，即黑素细胞和肠神经系统。为了评估EDN3/EDNRB信号通路能够选择性作用于这些NC衍生物的机制，我们研究了EDNRB基因在禽胚中的时空表达模式，禽胚是一种对NC发育进行了广泛研究的模型。为此，我们克隆了哺乳动物EDNRB cDNA的鹌鹑同源物。在神经轴各水平的NC细胞从神经管迁出之前及迁出过程中，均有EDNRB转录本存在。在发育后期，该受体在包括肠神经系统在内的外周神经系统中仍大量表达。在之前的一项研究中，我们发现当NC细胞处于多能阶段时，EDN3能显著增强其增殖。我们提出，EDN3或EDNRB基因失活的选择性作用是由于黑素细胞和肠神经系统前体都必须从数量相对较少但必须大量扩增的前体细胞群体中定殖到较大的胚胎区域（皮肤和肠道）。因此可以理解，NC细胞的一种促生长途径出现缺陷时，对远距离迁移细胞的有害影响比对像感觉和交感神经节那样在神经原基附近发育的NC衍生物的影响更大。
