DISRUPTION OF GASTRULATION MOVEMENTS IN XENOPUS BY A DOMINANT-NEGATIVE MUTANT FOR C-CADHERIN

DISRUPTION OF GASTRULATION MOVEMENTS IN XENOPUS BY A DOMINANT-NEGATIVE MUTANT FOR C-CADHERIN
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DOI:
10.1006/dbio.1995.1288
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发表时间:
1995-10-01
影响因子:
2.7
通讯作者:
GUMBINER, BM
GUMBINER, BM
中科院分区:
生物学3区
文献类型:
--
作者:
LEE, CH;GUMBINER, BM

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非洲爪蟾的原肠胚形成过程中,大量的细胞重排和运动使未分化的细胞球转变为具有明显体轴的组织良好的细长胚胎。由于细胞粘附被认为在组织形态发生过程中发挥了重要作用,我们研究了C-钙粘蛋白,主要的细胞-细胞粘附分子在非洲爪蟾,原肠胚运动的潜在作用。构建了由胞外和跨膜结构域组成但缺乏胞质尾区(Ctrunc)的缺失突变体,以作为内源性蛋白的显性负抑制剂。在体外转录的Ctrunc mRNA注射到前瞻性的背内卷边缘区,该地区经历了最广泛的运动,造成了可重复的缺陷原肠胚。缺陷,无法完成复旧和关闭胚孔,是钙粘蛋白特异性的,因为它可以通过表达全长C-钙粘蛋白来挽救。Ctrunc似乎也抑制从注射胚胎分离的动物帽外植体的形态发生运动。Ctrunc的表达似乎并没有干扰胚胎发育原肠胚缺陷的诱导过程,因为它们形成了完整的轴向结构,包括完整的头部和脊索。这些结果表明,C-钙粘蛋白在非洲爪蟾原肠胚运动中起着至关重要的作用,他们支持的假设,钙粘蛋白可以介导组织形态发生过程中的细胞重排。(C)出版社:Academic Press
Gastrulation in Xenopus laevis transforms a ball of undifferentiated cells into a well-organized elongated embryo with a distinct body axis, as a result of extensive cell rearrangements and movements. Since cell adhesion is thought to play an important role during tissue morphogenesis, we investigated the potential role for C-cadherin, a primary cell-cell adhesion molecule in Xenopus, in gastrulation movements. A deletion mutant consisting of the extracellular and transmembrane domains but lacking the cytoplasmic tail (Ctrunc) was constructed to act as a dominant-negative inhibitor of the endogenous protein. Injection of in vitro transcribed Ctrunc mRNA into the prospective dorsal involuting marginal zone, the region that undergoes the most extensive movements, caused a reproducible defect in gastrulation. The defect, an inability to complete involution and close the blastopore, was cadherin-specific, because it could be rescued by expressing full length C-cadherin. Ctrunc also seems to inhibit morphogenetic movements of animal cap explants isolated from injected embryos. Expression of Ctrunc did not appear to interfere with inductive processes in the embryos that developed gastrulation defects, because they formed complete axial structures, including a complete head and notochord. These results demonstrate that C-cadherin plays a critical role in Xenopus laevis gastrulation movements, and they support the hypothesis that cadherins can mediate cellular rearrangements during tissue morphogenesis. (C) 1995 Academic Press, Inc.