SIGNAL TRANSDUCTION IN VERTEBRATE EMBRYOGENESIS

描述（改编自研究者摘要）： 脊椎动物发育是信号和信号的同一性 转导机制，建立的位置和极性的 胚轴 在两栖动物中，Wnt途径中的蛋白质，包括 GSK-3、β-catenin和APC在这一过程中发挥重要作用。 类似 在哺乳动物发育中的作用尚未确定。 校长 研究人员和他的同事已经表征了小鼠“融合”基因， 似乎是Wnt途径的一种新的调节剂。 初步数据 表明融合作为轴发展的负调节剂， 在Wnt通路中发挥作用。 现在的首席研究员 建议进一步研究融合在胚胎发育中的作用， 及其调节Wnt信号传导的分子机制 通路 为了实现这一目标，列出了五个具体目标。 第一 是使用非洲爪蟾胚胎研究融合在 通过注射野生型或突变体的背轴的特化 与Wnt通路或其他信号通路中的因子融合。 的 第二个目标将表征大小，亚细胞位置，共价键， 修饰和融合蛋白在胚胎发生过程中的表达， 可能由次要转录本编码的较小蛋白质，以及两个 自发突变体 第三个目标是研究融合如何在 通过研究其物理和功能相互作用， 其他蛋白质。 第四个目标将进一步描述隐性 两个突变等位基因引起的胚胎缺陷， Fused在小鼠胚胎发生中的作用。 最后，新型突变体和 将产生转基因小鼠以研究融合蛋白在小鼠中的作用。 胚胎发生

DESCRIPTION (adapted from investigator's abstract): A basic question in vertebrate development is the identity of the signals and signal transduction mechanisms that establish the position and polarity of the embryonic axes. In amphibians, the proteins in the Wnt pathway, including GSK-3, beta-catenin, and APC play important roles in this process. Similar roles in mammalian development have yet to be established. The Principal Investigator and his colleaques have characterized mouse "Fused" gene, which appears to be a novel regulator of the Wnt pathway. Preliminary data suggests that Fused acts as a negative regulator of axis development and exerts its effects in the Wnt pathway. The Principal Investigator now proposes to further investigate the role of Fused in embryonic development, and the molecular mechanisms by which it regulates signaling in the Wnt Pathway. To accomplish this goal, five specific aims are listed. The first is to use Xenopus laevis embryos to study the role of Fused in the specification of the dorsal axis through injection of wild type or mutant Fused with factors in the Wnt pathway or in other signaling pathways. The second aim will characterize the sizes, subcellular location, covalent modification, and expression during embryogenesis of the Fused proteins, a smaller protein potentially encoded by a minor transcript, and two spontaneous mutants. The third aim is to investigate how Fused functions at the molecular level by studying its physical and functional interaction with other proteins. The fourth aim will characterize further the recessive embryonic defects caused by two mutants alleles in an effort to understand the role of Fused in mouse embryogenesis. Finally, new types of mutants and transgenic mice will be generated to study the role of Fused in mouse embryogenesis.