Clouthier D E, Hosoda K, Richardson J A, Williams S C, Yanagisawa H, Kuwaki T, Kumada M, Hammer R E, Yanagisawa M
Howard Hughes Medical Institute, Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235, USA.
Development. 1998 Mar;125(5):813-24. doi: 10.1242/dev.125.5.813.
Neural crest cells arise in the dorsal aspect of the neural tube and migrate extensively to differentiate into a variety of neural and non-neural tissues. While interactions between neural crest cells and their local environments are required for the proper development of these tissues, little information is available about the molecular nature of the cell-cell interactions in cephalic neural crest development. Here we demonstrate that mice deficient for one type of endothelin receptor, ETA, mimic the human conditions collectively termed CATCH 22 or velocardiofacial syndrome, which include severe craniofacial deformities and defects in the cardiovascular outflow tract. We show that ETA receptor mRNA is expressed by the neural crest-derived ectomesenchymal cells of pharyngeal arches and cardiac outflow tissues, whereas ET-1 ligand mRNA is expressed by arch epithelium, paraxial mesoderm-derived arch core and the arch vessel endothelium. This suggests that paracrine interaction between neural crest-derived cells and both ectoderm and mesoderm is essential in forming the skeleton and connective tissue of the head. Further, we find that pharyngeal arch expression of goosecoid is absent in ETA receptor-deficient mice, placing the transcription factor as one of the possible downstream signals triggered by activation of the ETA receptor. These observations define a novel genetic pathway for inductive communication between cephalic neural crest cells and their environmental counterparts.
神经嵴细胞起源于神经管的背侧，并广泛迁移以分化为多种神经和非神经组织。虽然神经嵴细胞与其局部环境之间的相互作用对于这些组织的正常发育是必需的，但关于头部神经嵴发育中细胞间相互作用的分子本质的信息却很少。在这里，我们证明，缺乏一种内皮素受体ETA的小鼠模拟了统称为CATCH 22或心脏颜面综合征的人类病症，这些病症包括严重的颅面畸形和心血管流出道缺陷。我们表明，ETA受体mRNA由咽弓和心脏流出组织的神经嵴衍生的外胚间充质细胞表达，而ET-1配体mRNA由弓上皮、轴旁中胚层衍生的弓核心和弓血管内皮表达。这表明神经嵴衍生细胞与外胚层和中胚层之间的旁分泌相互作用对于形成头部的骨骼和结缔组织至关重要。此外，我们发现ETA受体缺陷小鼠中咽弓的goosecoid表达缺失，这使得该转录因子成为由ETA受体激活触发的可能的下游信号之一。这些观察结果定义了一种新的遗传途径，用于头部神经嵴细胞与其周围环境之间的诱导性通讯。
