Regulation of call adhesion in Xenopus

描述（由申请人提供）：在非洲爪蟾原肠胚形成期间，胚层内和胚层之间粘附特性的调节控制细胞-细胞和细胞-细胞外基质相互作用，以调节形态发生。细胞粘附分子如钙粘蛋白、原钙粘蛋白和整合素参与细胞粘附和细胞运动的差异调节。已知参与中胚层图案形成的生长因子如Wnt和激活素/nodal也影响中胚层形态发生和细胞形状。本项目的重点是揭示FLRT 3（Fibronectin Leucine-rich Repeat Transmembrane protein 3）在非洲爪蟾早期形态发生中的分子功能。在揭示FLRTS功能的过程中，我们做了以下有趣的观察：首先，FLRT 3和Rnd 1在原肠胚期胚胎的退化边缘细胞中共表达。其次，FLRT 3的过表达阻断了被处理细胞中钙粘蛋白介导的粘附，这种作用需要Rnd 1的存在。第三，FLRT 3与Rndl物理相互作用。我们现在提出解决以下问题，以阐明TGF-β信号介导的形态发生事件背后的分子机制：目的1：FLRT 3和Rnd 1的功能如何调节原肠胚运动？目标2：FLRT 3如何与Rnd 1相互作用？目标3：FLRT 3和Rnd 1如何调节钙粘蛋白介导的粘附？目的4：还有哪些分子介导FLRT 3和Rndl信号传导？该提案概述了试图描绘FLRT 3跨膜蛋白的功能，从细胞外水平向下通过影响细胞粘附的细胞内信号事件。许多研究已经将小GTP酶和粘附分子如钙粘蛋白的异常表达与肿瘤发生和转移联系起来。由于肿瘤的发展往往平行于胚胎发育的过程中，快速细胞增殖和广泛的细胞运动，我们的工作可能会提供直接相关的更好地了解肿瘤发生。

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.