The Wnt Pathway and Inductive Competence in Early Xenopus Development

非洲爪蟾早期发育中的 Wnt 通路和归纳能力

• 批准号: 0110893
• 负责人: Paul Wilson
• 金额: $ 30万
• 依托单位: Joan and Sanford I. Weill Medical College of Cornell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0110893&HistoricalAwards=false
• 关键词: Wnt; Pathway; Inductive; Competence; Early

0110893WilsonInductive signals between cell populations govern much of embryonic development. A central feature of these interactions is changing competence: the response of cells to particular signaling ligands evolves in a complex and precisely regulated manner. The long-term goal of the proposed research is to understand the molecular basis of competence, using changing responses to Wnt signaling in early Xenopus development as a model. In the first hours of Xenopus development, activation of the Wnt signaling pathway drives formation of the dorsal axis; only a few hours later, this response is lost, and the pathway instead functions in mesodermal and neural patterning. The objectives of the current project are to understand why an important target gene, siamois, is activated by early but not by late Wnt signaling, and to tie competence of the Wnt pathway to induce this gene to the broader embryological response, dorsal axis formation. Using a simple promoter-reporter assay, the siamois promoter will be analyzed to identify sequence elements important in the loss of Wnt responsiveness at later stages. Competence of siamois itself to induce a dorsal axis will then be examined using inducible activated and inhibitory versions of siamois, thus linking the regulation of this gene to axis induction competence. Both aims will make use of a newly developed tool for inducible stimulation of Wnt responses, consisting of a dexamethasone-inducible, activated form of XTCF3, a DNA-binding protein known to mediate transcriptional responses to Wnt signaling. This work will contribute to elucidating the mechanism of inductive competence, an important and long-standing problem in developmental biology.

0110893细胞种群之间的WWILSONINDUCTIVES信号控制着大部分胚胎发育。 这些相互作用的主要特征是改变能力：细胞对特定信号配体的反应以复杂而精确的调节方式演变。 拟议的研究的长期目标是使用对早期Xenopus开发中Wnt信号的反应的改变作为模型，以了解能力的分子基础。 在爪蟾发育的头几个小时中，Wnt信号通路的激活驱动背轴的形成； 仅几个小时后，这种反应就会丢失，而途径则在中胚层和神经模式中起作用。 当前项目的目标是了解为什么重要的靶基因siamois是通过早期但不是Wnt信号传导激活的，并不得将WNT途径的能力诱导该基因诱导该基因的能力，从而诱导更广泛的胚胎轴，背轴形成。使用简单的启动子培养剂测定法，将分析Siamois启动子，以确定对后期WNT响应性丧失的序列元件。 然后，将使用诱导的激活和抑制性版本的暹罗族对暹罗本身诱导背轴的能力进行检查，从而将该基因的调节与轴诱导能力联系起来。 这两个目标都将利用一种新开发的工具来诱导Wnt响应，该响应由XTCF3的地塞米松诱导，活化形式组成，XTCF3是一种DNA结合蛋白，已知介导对WNT信号的转录响应。 这项工作将有助于阐明归纳能力的机制，这是发育生物学中的重要且长期存在的问题。