Twisted Gastrulation Gene in Vertebrate Development

脊椎动物发育中扭曲的原肠胚形成基因

• 批准号: 6683394
• 负责人: CHENBEI CHANG
• 金额: $ 24.8万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6683394
• 关键词: SDS polyacrylamide gel electrophoresis; Xenopus; autoradiography; biological signal transduction; bone morphogenetic proteins; cell migration; chimeric proteins; ectoderm; embryogenesis; endopeptidases; glycoproteins; polymerase chain reaction; protein protein interaction; protein structure function; vertebrate embryology; western blottings

DESCRIPTION (provided by applicant): The proposed research is to understand the molecular mechanisms through which a soluble protein, twisted gastrulation (Tsg), regulates the early vertebrate embryogenesis. A main focus will be on the strategies that Tsg uses to modify the signals from the bone morphogenetic proteins (BMPs). BMPs are versatile growth factors that control multiple processes during early vertebrate development, such as the dorsal-ventral patterning and the morphogenesis and the organogenesis of various organs. The activities of BMPs are regulated by many secreted factors, including the BMP antagonist chordin and the chordin inactivating enzymes tolloid/Xolloid/BMP1. Recently, a new soluble component, Tsg, has been identified, which seems to modulate the BMP signals in a unique way. Tsg can block the BMP function in both zebrafish and Xenopus; it, however, also induces some defects in frogs that partially mimic the phenotypes of the BMP overexpression. The mechanisms for the actions of Tsg in vivo are not well understood. Preliminary studies performed in this laboratory demonstrate that Tsg is required both in the dorsal and in the ventral regions for normal frog embryogenesis; Tsg may cooperate with chordin dorsally to control the dorsoanterior development. Tsg is detected at the cell periphery in vivo, and overexpression of Tsg may affect the cell movement. The proposed research will test the hypotheses that Tsg, in complex with chordin and BMPs, may be involved in the transportation of the BMP ligands and thus modulate the BMP signals; and Tsg may regulate the vertebrate development through its influence on the cell migratory behaviors. In aim 1, the in vivo interaction of Tsg, chordin, tolloid-related proteases and BMPs will be further studied at the molecular level by the loss-of-function approach. In aim 2, the distribution of the BMPs in the ectoderm of early frog embryos in the presence or the absence of Tsg and/or chordin will be analyzed. In aim 3, the influence of Tsg on cell movement will be examined. In aim 4, the direct interactions of Tsg with different BMPs and other unidentified factors will be studied. The results from these experiments will provide important clues on the mechanisms of the Tsg function, and will contribute greatly to our understanding on regulation of the BMP signals by a network of the extracellular proteins.

描述（由申请人提供）：拟议的研究旨在了解可溶性蛋白质扭曲原肠胚形成（Tsg）调节早期脊椎动物胚胎发生的分子机制。主要关注点是 Tsg 用于修改骨形态发生蛋白 (BMP) 信号的策略。 BMP 是一种多功能生长因子，可控制早期脊椎动物发育过程中的多个过程，例如背腹模式以及各种器官的形态发生和器官发生。 BMP 的活性受到许多分泌因子的调节，包括 BMP 拮抗剂 Chordin 和 Chordin 失活酶 Tolloid/Xolloid/BMP1。最近，一种新的可溶性成分 Tsg 被发现，它似乎以独特的方式调节 BMP 信号。 Tsg 可以阻断斑马鱼和爪蟾的 BMP 功能；然而，它也会在青蛙中诱导一些缺陷，部分模仿 BMP 过度表达的表型。 Tsg 在体内的作用机制尚不清楚。该实验室进行的初步研究表明，正常青蛙胚胎发生的背部和腹侧区域都需要 Tsg； Tsg 可能与背部的脊索蛋白合作来控制背前部的发育。 Tsg 在体内的细胞外周检测到，Tsg 的过度表达可能会影响细胞运动。拟议的研究将测试以下假设：Tsg 与脊索蛋白和 BMP 复合，可能参与 BMP 配体的运输，从而调节 BMP 信号； Tsg可能通过影响细胞迁移行为来调节脊椎动物的发育。在目标 1 中，将通过功能丧失方法在分子水平上进一步研究 Tsg、chordin、tolloid 相关蛋白酶和 BMP 的体内相互作用。在目标 2 中，将分析在存在或不存在 Tsg 和/或脊索蛋白的情况下早期青蛙胚胎外胚层中 BMP 的分布。在目标 3 中，将检查 Tsg 对细胞运动的影响。在目标 4 中，将研究 Tsg 与不同 BMP 和其他未识别因素的直接相互作用。这些实验的结果将为 Tsg 功能机制提供重要线索，并将极大地有助于我们理解细胞外蛋白网络对 BMP 信号的调节。