Regulation of call adhesion in Xenopus

描述（由申请人提供）：在非洲爪蟾原肠胚形成过程中，胚层内部和胚层之间的粘附特性调节控制细胞间和细胞间基质的相互作用，从而调节形态发生。细胞粘附分子，如钙粘蛋白、原钙粘蛋白和整合素，参与了细胞粘附和细胞运动的差异调节。已知参与中胚层模式的生长因子，如Wnt和激活素/结也影响中胚层形态发生和细胞形状。本项目的重点是揭示FLRT3（富纤维连接蛋白亮氨酸重复跨膜蛋白3）在爪蟾早期形态发生中的分子功能。在揭示FLRTS功能的过程中，我们得到了以下有趣的观察结果：首先，FLRT3和Rnd1在原胚期胚胎的内翻边缘细胞中共表达。其次，FLRT3的过表达阻断了处理细胞中钙粘蛋白介导的粘附，这种作用需要Rnd1的存在。第三，FLRT3与Rndl进行物理交互。我们现在提出解决以下问题，以阐明TGF-B信号介导的形态发生事件背后的分子机制：目的1:FLRT3和Rnd1如何调节原肠泌乳运动？目的2:FLRT3如何与Rnd1相互作用？目标3。FLRT3和Rnd1如何调节钙粘蛋白介导的粘附？目的4：还有哪些分子介导FLRT3和Rndl信号转导？本提案概述了FLRT3跨膜蛋白从细胞外水平到影响细胞粘附的细胞内信号事件的功能。许多研究已经将小gtpase和粘附分子（如钙粘蛋白）的异常表达与肿瘤的发生和转移联系起来。由于肿瘤的发展在细胞快速增殖和广泛的细胞运动方面往往与胚胎发育过程相似，因此我们的工作可能为更好地理解肿瘤发生提供直接关联。

DESCRIPTION (provided by applicant): During Xenopus gastrulation, the modulation of adhesive properties within and between the germ layers controls cell-cell and cell-extracellular matrix interactions to regulate morphogenesis. Cell adhesion molecules such as cadherins, protocadherins and integrins have been implicated in the differential regulation of cell adhesion and cell movement. Growth factors known to be involved in mesoderm patterning such as Wnt and activin/nodal also influence mesodermal morphogenesis and cell shape. The focus of this project is to uncover the molecular function of FLRT3 (Fibronectin Leucine-rich Repeat Transmembrane protein 3) in early Xenopus morphogenesis. In the process of uncovering FLRTS's function, we have made the following intriguing observations: First, FLRT3 and Rnd1 are coexpressed in the involuting marginal cells of gastrula stage embryos. Second, overexpression of FLRT3 blocks cadherin-mediated adhesion in the treated cells and this effect requires the presence of Rnd1. Third, FLRT3 interacts physically with Rndl. We now propose to address the following questions to elucidate the molecular mechanisms behind the morphogenetic events mediated by TGF-B signaling: Aim 1: How do FLRT3 and Rnd1 function to regulate gastrulation movements? Aim 2: How does FLRT3 interact with Rnd1? Aim 3. How is cadherin-mediated adhesion modulated by FLRT3 and Rnd1? Aim 4: What other molecules mediate FLRT3 and Rndl signaling? This proposal outlines an attempt to delineate the function of the FLRT3 transmembrane protein from the extracellular level down through the intracellular signaling events that affect cell adhesion. Numerous studies have linked aberrant expression of small GTPases and adhesion molecules such as cadherins to oncogenesis and metastasis. As the development of tumors often parallels the process of embryonic development in terms of rapid cell proliferation and extensive cellular movements, our work may provide direct relevance for a better understanding of tumorigenesis.