Genetics Analysis of FGF Function in the Mouse

描述(研究人员摘要)：成纤维细胞生长因子信号分子家族 在脊椎动物的许多方面起着核心的调节作用 胚胎发生，也是重要的控制生理和 成人的病理过程。有确凿的证据表明 以前的遗传学研究表明，成纤维细胞生长因子家族中的一个成员FGF8是必不可少的 处于胚胎发育的多个阶段。这项建议主要集中在三个关键方面 依赖于FGF8信号的发育过程：左右轴- 决定、肢体发育和肾脏发育。这些实验 旨在用遗传学的方法来阐明基因的功能 FgJ8和其他成纤维细胞生长因子家族成员参与了这些过程。他们利用 小鼠基因功能分析方法的最新进展，包括 特定组织中的条件性功能丧失和获得，以及报道 基因表达和蛋白质分布的等位基因。每一个特定的目标 包括开发新的转基因小鼠品系，不仅将 使回答特定问题和测试关于这些问题的假设成为可能 特定的过程，但也将是非常有用的研究工具 脊椎动物在实验室中发育的许多其他方面 科学界。这些研究的结果应该会提供更深层次的 对建立基本机构计划所涉及的机制的理解 以及四肢和肾脏的形成。所获得的信息将是 与理解人类发育机制和病因学有关 人类先天缺陷、慢性病和各种形式的成人疾病 是在怀孕期间产生的。

DESCRIPTION (Investigator's abstract): The FGF family of signaling molecules plays a central role in the regulation of many aspects of vertebrate embryogenesis, and is also important in the control of physiological and pathological processes in the adult. There is substantial evidence from previous genetic studies that one member of the FGF family, FGF8, is essential at multiple stages of embryogenesis. This proposal is focused on three key developmental processes that are dependent on FGF8 signaling: left-right axis- determination, limb development, and kidney development. The experiments proposed are aimed at using a genetic approach to elucidate the function of FgJ8 and other FGF family members in these processes. They take advantage of recent advances in methods for analyzing gene function in mice, including conditional loss- and gain-of-function in specific tissues, and reporter alleles for gene expression and protein distribution. Each Specific Aim includes the development of new lines of transgenic mice that will not only make it possible to answer specific questions and test hypotheses about these particular processes, but will also be extremely useful as tools for studies of many other aspects of vertebrate development in laboratories throughout the scientific community. The results of these studies should provide a deeper understanding of the mechanisms involved in establishing the basic body plan and the formation of limbs and kidneys. The information obtained will be relevant to understanding the mechanism of human development and the etiology of human birth defects, chronic diseases, and various forms of adult disease that originate during gestation.