Cadherin-based Actin Assembly in the Xenopus Embryo

描述（由申请人提供）：该提案验证了一个假设，即经典钙粘蛋白除了在细胞-细胞粘附中已知的作用外，还通过控制皮质肌动蛋白的组装来控制脊椎动物胚胎中形态发生组织的运动。钙粘蛋白是一个大家族的蛋白质，它们在胚胎形成的不同组织中以不同的组合表达。我们提出，不同钙粘蛋白的组合，以及它们表达的不同细胞环境，共同产生具有不同运动和粘附特性的皮质肌动蛋白网络。这导致了胚胎中出现的组织形状的特征性差异。这一假设得到了广泛的初步数据和已发表的研究成果的支持，将在早期非洲爪蟾胚胎外胚层（起源于囊胚的动物区域）中进行测试。我们之前已经证明，囊胚皮层肌动蛋白丝网络对整个胚胎的整体形状和刚性至关重要，它需要c -钙粘蛋白在细胞表面的表达。随着外胚层的分化，神经和非神经外胚层表达不同的钙粘蛋白组合，这些表达的变化伴随着组织运动的剧烈变化。我们将通过在错误的组织中操纵单个钙粘蛋白或成分结构域的表达来验证中心假设，比较与它们结合的肌动蛋白组装蛋白，并测试与不同钙粘蛋白不同结合的蛋白的功能。在以前的工作中，我们发现磷脂的信号传导是囊胚皮层肌动蛋白组装的必要条件。我们将测试这一假设，即它仍然需要肌动蛋白组装外胚层组织源自囊胚。

DESCRIPTION (provided by applicant): This proposal tests the hypothesis that the classical cadherins, in addition to their known role in cell-cell adhesion, also control morphogenetic tissue movements in the vertebrate embryo, by controlling the assembly of cortical actin. Cadherins are a large family of proteins, which are expressed in different combinations in different tissues of the embryo as they form. We propose that the combination of different cadherins, and the different cellular contexts in which they are expressed, together generate cortical actin networks with different motile and adhesive properties. This results in the characteristic differences in tissue shapes that arise in the embryo. This hypothesis, which is supported by extensive preliminary data and published work, will be tested in the early Xenopus embryonic ectoderm, which arises from the animal region of the blastula. We have shown previously that the cortical actin filament network in the blastula, which is essential for overall shape and rigidity of the whole embryo, requires the expression of C-cadherin on the cell surface. As the ectoderm differentiates, the neural and non-neural ectoderm express different combinations of cadherins, and dramatic changes in tissue movement accompany these changes in expression. We will test the central hypothesis by manipulating the expression of individual cadherins, or component domains, in the wrong tissues, compare the actin assembly proteins that bind to them, and test the functions of those that bind differentially to different cadherins. In previous work, we showed that signaling by phospholipids is essential for cortical actin assembly in the blastula. We will test the hypothesis that it continues to be required for actin assembly in the ectodermal tissues derived from the blastula. PUBLIC HEALTH RELEVANCE: This project aims to identify the molecular mechanisms that coordinate cell adhesion and cell motility as the organs of the body first form. Many birth defects are caused by failure of cell adhesion and tissue movement, and so a molecular understanding of the way they occur is important and timely.