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: 7225541
• 负责人: CHENBEI CHANG
• 金额: $ 24.75万
• 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 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7225541
• 关键词: Twisted; Gastrulation; Gene; Vertebrate; Development

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）：拟议的研究是为了了解可溶性蛋白（TSG）调节早期脊椎动物胚胎发生的分子机制。主要重点将是TSG用来修改骨形态发生蛋白（BMP）的信号的策略。 BMP是多功能生长因子，在早期脊椎动物发育过程中控制多个过程，例如背腹模式以及各种器官的形态发生和器官发生。 BMP的活性受许多分泌因素的调节，包括BMP拮抗剂Chordin和Chordin灭活酶Toloid/Xolloid/BMP1。最近，已经确定了一种新的可溶性组件TSG，它似乎以独特的方式调节BMP信号。 TSG可以阻止斑马鱼和Xenopus中的BMP功能。然而，它还诱发了青蛙中某些缺陷，这些缺陷部分模仿了BMP过表达的表型。 TSG在体内作用的机制尚不清楚。在该实验室进行的初步研究表明，在背侧和腹侧地区需要进行TSG，以使正常的青蛙胚胎发生。 TSG可以背侧与Chordin合作，以控制多头骨的发展。在体内的细胞周围检测到TSG，TSG的过表达可能会影响细胞运动。拟议的研究将检验的假设，即与Chordin和BMP复杂的TSG可能参与BMP配体的运输，从而调节BMP信号。 TSG可以通过对细胞迁移行为的影响来调节脊椎动物的发育。在AIM 1中，将通过功能丧失方法在分子水平上进一步研究TSG，Chordin，与Toloid相关的蛋白酶和BMP的体内相互作用。在AIM 2中，将分析BMP在存在或不存在TSG和/或Chordin的早期青蛙胚胎外胚层中的分布。在AIM 3中，将检查TSG对细胞运动的影响。在AIM 4中，将研究TSG与不同的BMP和其他未知因素的直接相互作用。这些实验的结果将提供有关TSG函数机制的重要线索，并将极大地理解通过细胞外蛋白网络对BMP信号的调节。