Regulation of call adhesion in Xenopus

非洲爪蟾呼叫粘附的调节

基本信息

批准号：
7924292
负责人：
Ken W.Y. Cho
金额：
$ 9.42万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7924292
关键词：
Activins Address Adhesions Adhesives Affect Amphibia Animal Cap Area Attention Biological Models Cadherins Cell Adhesion Cell Adhesion Molecules Cell Proliferation Cell Shape Cell surface Cells Comprehension DNA Microarray Chip Data Development Ectoderm Embryo Embryology Embryonic Development Event Extracellular Matrix Fibroblast Growth Factor Fibronectins Gastrula Gene Targeting Genes Germ Layers Goals Growth Factor Integral Membrane Protein Integrins Leucine-Rich Repeat Link Mediating Mesoderm Molecular Monomeric GTP-Binding Proteins Morphogenesis Motion Movement Mutation Nature Neoplasm Metastasis Nodal Pattern Play Population Process Property Protein Family Proteins Regulation Research Personnel Risk Role Series Signal Transduction Signaling Molecule Staging Work Xenopus base cell motility extracellular gastrulation member overexpression parallel processing programs tumor tumorigenesis

项目摘要

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.

描述（由申请人提供）：在非洲爪蟾原肠胚形成期间，胚层内和胚层之间的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与细胞粘附和细胞运动的差异调节有关。已知参与中胚层模式形成的生长因子（例如 Wnt 和激活素/nodal）也会影响中胚层形态发生和细胞形状。该项目的重点是揭示 FLRT3（富含纤维连接蛋白亮氨酸的重复跨膜蛋白 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，我们进行了以下有趣的观察：首先，FLRT3和Rnd1在原肠胚阶段胚胎的退化边缘细胞中共表达。其次，FLRT3 的过度表达会阻断处理细胞中钙粘蛋白介导的粘附，而这种效应需要 Rnd1 的存在。第三，FLRT3 与 Rndl 进行物理交互。我们现在建议解决以下问题，以阐明 TGF-B 信号介导的形态发生事件背后的分子机制：目标 1：FLRT3 和 Rnd1 如何发挥调节原肠胚形成运动的作用？目标 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？目标 4：还有哪些其他分子介导 FLRT3 和 Rndl 信号传导？该提案概述了从细胞外水平到影响细胞粘附的细胞内信号传导事件来描述 FLRT3 跨膜蛋白功能的尝试。许多研究已将小 GTP 酶和粘附分子（例如钙粘蛋白）的异常表达与肿瘤发生和转移联系起来。由于肿瘤的发展通常与胚胎发育的过程在快速细胞增殖和广泛的细胞运动方面平行，因此我们的工作可能为更好地理解肿瘤发生提供直接相关性。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Finding partners: how BMPs select their targets.

寻找合作伙伴：BMP 如何选择目标。

DOI：
发表时间：
2009-06
期刊：
影响因子：
0
作者：
Blitz, Ira L;Cho, Ken W Y
通讯作者：
Cho, Ken W Y

Ventral closure, headfold fusion and definitive endoderm migration defects in mouse embryos lacking the fibronectin leucine-rich transmembrane protein FLRT3.

缺乏富含纤连蛋白亮氨酸的跨膜蛋白 FLRT3 的小鼠胚胎中的腹侧闭合、头折融合和定形内胚层迁移缺陷。

DOI：
发表时间：
2008-06-01
期刊：
影响因子：
2.7
作者：
Maretto, Silvia;Müller, Pari;Aricescu, A Radu;Cho, Ken W Y;Bikoff, Elizabeth K;Robertson, Elizabeth J
通讯作者：
Robertson, Elizabeth J

Site-specific transgene integration in the human genome catalyzed by phiBT1 phage integrase.

由 phiBT1 噬菌体整合酶催化的人类基因组中的位点特异性转基因整合。