GAP JUNCTIONS DURING EMBRYONIC AXIS FORMATION

这个项目的长期目标是理解规则 和缝隙连接通讯(GJC)在早期胚胎中的作用 发展。该提案旨在1)确定β-连环蛋白 调节GJC，II)通过对GJC的分析来研究GJC的调节 缝隙连接蛋白-38在正常和β-连环蛋白中的表达及定位 以及III)研究连接蛋白的发育功能-- 38在早期胚胎中的表达，并探讨其在细胞黏附中的作用。差距 将使用非洲爪哇胚胎模型来研究连接调节 系统。母体表达β-连环蛋白或连接蛋白-38将是 用反义寡核苷酸特异性阻断。GJC将成为 荧光染料微量注射监测及染料迁移分析 在早期胚胎的卵裂球之间。GJC对于正常生活是必不可少的 缺乏连接蛋白-43的转基因小鼠心脏发育严重 右心室的缺陷(Reaume等人，1995)。科学267：1831)。 另一种发展为心脏缺陷的患者，内脏心房异位 显示连接蛋白-43基因的高突变率(Britz-Cunningham et 等人，1995年。NEJM 332：1323)，而那些表现出X连锁的 神经病，夏科-玛丽-图斯病，连接蛋白-32发生突变 基因(Bergoffer等人，《科学》262：2039)。此外，连接蛋白-26还具有 被确定为可能的肿瘤抑制因子，这表明缺口 连接通讯参与细胞生长控制(Lee等人， 1992年。J.细胞生物学。118：1213)。考虑到正常状态之间的这种关系 发展与交汇性交际--兼论交际法的规律性 缝隙连接应该有助于更好地理解 控制正常生长和胚胎发育。

The long-term objective of this project is to understand the regulation and function of gap junctional communication (GJC) during early embryonic development. This proposal aims to 1) determine whether beta-catenin regulates GJC, ii) investigate the regulation of GJC by analysis of the expression and localization of connexin-38 in normal and beta-catenin- deficient embryos, and iii) study the developmental function of connexin- 38 in the early embryo and investigate its role in cell adhesion. Gap junction regulation will be studied using the Xenopus embryonic model system. Maternal expression of beta-catenin or connexin-38 will be specifically blocked using anti-sense oligodeozynucleotides. GJC will be monitored by fluorescent dye microinjection and analysis of dye transfer between blastomeres of the early embryo. GJC is essential for normal heart development as transgenic mice lacking connexin-43 develop severe defects of the right ventricle (Reaume et al., 1995. Science 267: 1831). Patients with another development heart defect, visceroatrial heterotaxia show a high mutation rate in the connexin-43 gene (Britz-Cunningham et al., 1995. NEJM 332: 1323), while those exhibiting the X-linked neuropathy, Charcot-Marie-Tooth disease, have mutations in the connexin-32 gene (Bergoffer et al., Science 262: 2039). In addition, connexin-26 has been identified as a possible tumor suppressor, suggesting that gap junctional communication is involved in cell growth control (Lee et al., 1992. J. Cell Biol. 118: 1213). Given this relationship between normal development and junctional communication, an analysis of the regulation of gap junctions should lead to a better understanding of mechanisms which control normal growth and embryonic development.