Bradley R S, Espeseth A, Kintner C
Salk Institute for Biological Studies, San Diego, California 92186, USA.
Curr Biol. 1998 Mar 12;8(6):325-34. doi: 10.1016/s0960-9822(98)70132-0.
The assembly of complex tissues during embryonic development is thought to depend on differential cell adhesion, mediated in part by the cadherin family of cell-adhesion molecules. The protocadherins are a new subfamily of cadherins; their extracellular domains comprise cadherin-like repeats but their intracellular domains differ significantly from those of classical cadherins. Little is known about the ability of protocadherins to mediate the adhesion of embryonic cells, or whether they play a role in the formation of embryonic tissues.
We report the isolation and characterization of a novel protocadherin, termed NF-protocadherin (NFPC), that is expressed in Xenopus embryos. NFPC showed a striking pattern of expression in early embryos, displaying predominant expression within the deep, sensorial layer of the embryonic ectoderm and in a restricted group of cells in the neural folds, but was largely absent from the neural plate and surrounding placodal regions. Ectopic expression in embryos demonstrated that NFPC could mediate cell adhesion within the embryonic ectoderm. In addition, expression of a dominant-negative form of NFPC disrupted the integrity of embryonic ectoderm, causing cells in the deep layer to dissociate, though leaving the outer layer relatively intact.
Our results indicate that NFPC is required as a cell-adhesion molecule during embryonic development, and its function is distinct from that of classical cadherins in governing the formation of a two-layer ectoderm. These results suggest that NFPC, and protocadherins in general, are involved in novel cell-cell adhesion mechanisms that play important roles in tissue histogenesis.
胚胎发育过程中复杂组织的组装被认为依赖于差异细胞黏附,这部分是由细胞黏附分子的钙黏蛋白家族介导的。原钙黏蛋白是钙黏蛋白的一个新亚家族;它们的细胞外结构域包含钙黏蛋白样重复序列,但其细胞内结构域与经典钙黏蛋白的结构域有显著差异。关于原钙黏蛋白介导胚胎细胞黏附的能力,或者它们是否在胚胎组织形成中发挥作用,人们了解甚少。
我们报告了一种新的原钙黏蛋白(称为NF-原钙黏蛋白,NFPC)的分离和特性,它在非洲爪蟾胚胎中表达。NFPC在早期胚胎中呈现出显著的表达模式,在胚胎外胚层的深层感觉层以及神经褶中的一组受限细胞中表达占主导,但在神经板和周围基板区域基本不存在。在胚胎中异位表达表明NFPC可以介导胚胎外胚层内的细胞黏附。此外,NFPC显性负性形式的表达破坏了胚胎外胚层的完整性,导致深层细胞解离,而外层相对保持完整。
我们的结果表明,NFPC在胚胎发育过程中作为一种细胞黏附分子是必需的,并且其功能在控制两层外胚层的形成方面与经典钙黏蛋白不同。这些结果表明,NFPC以及一般的原钙黏蛋白参与了在组织组织发生中起重要作用的新型细胞-细胞黏附机制。