MOLECULAR DETERMINANTS OF CHICK LIMB DEVELOPMENT

雏鸡肢体发育的分子决定因素

• 批准号: 2205506
• 负责人: Lee A. Niswander
• 金额: $ 10万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-29 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2205506
• 关键词: developmental genetics; histogenesis; limbs

This is a Shannon award providing partial support for the research projects that fall short of the assigned Institute's funding range but are in the margin of excellence. The Shannon award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. DESCRIPTION (Adapted from applicant's abstract): Dr. Niswander will test a model that proposes mutual interactions between the signals from the ridge, ZPA, and dorsal ectoderm, that serve to coordinate growth and pattern formation during limb development. She will focus on four outstanding questions related to embryonic limb development. How do these signals regulate each others activity? What genes are involved in establishing, and responding to, the ZPA and polarized ridge? How do cells interpret positional information? How does FGF signaling regulate biological responses in the limb? Specific Aim 1 is designed to address how Fgf4 is regulated by the endogenous ZPA. Further studies in this aim will identify genes that mediate establishment of the polarizing region and cell respecification. The studies in Specific Aim 2 will examine the regulation of Shh by FGF4 and the dorsal ectoderm and define the molecular nature of the dorsal ectoderm signal. Additional studies will explore how cells respond to SHH activity in defining their positional identity. In Specific Aim 3, the mechanism of FGF4 action will be characterized by analysis of the FGF receptor signal transduction pathway. Signaling through the receptor will be disrupted using a panel of FGF receptor mutations. The biochemical, molecular and cellular processes that are regulated by FGF in the limb will be analyzed, both in vitro and in vivo, to determine whether specific developmental events are disrupted. Downstream components of the FGF signaling pathway will be used to rescue the mutant phenotype and substrate proteins that relay the FGF signal will be identified.

这是香农奖，为研究提供部分支持 与指定研究所的资金范围相差的项目，但 处于卓越的范围。香农奖旨在提供 支持测试方法的可行性；开发进一步的测试 并完善研究技术；对可用的次要分析 数据集；或执行可以证明PI的离散项目 研究能力或增加本来有功的重量 应用。下面的摘要取自原始文档 由首席调查员提交。 描述（改编自申请人的摘要）：Niswander博士将 测试一个模型，该模型提出了来自来自的信号之间的相互作用 山脊，ZPA和背外胚层可用于协调生长和 肢体发育过程中的模式形成。她将专注于四个 与胚胎肢体发育有关的杰出问题。怎么办 这些信号互相调节活动？涉及哪些基因 在建立和回应ZPA和两极分化的山脊时？如何 细胞会解释位置信息吗？ FGF信号如何 调节肢体中的生物反应？ 特定目标1旨在解决FGF4如何受到FGF4的调节 内源性ZPA。以此目的的进一步研究将确定 中介建立偏振区域和细胞分解。 特定目标2中的研究将检查FGF4对SHH的调节 以及背外侧术语并定义背侧的分子特性 外皮信号。其他研究将探讨细胞如何响应 SHH活动定义其位置身份。在特定的目标3中 FGF4作用的机制将以FGF的分析为特征 受体信号转导途径。通过受体发出信号 使用FGF受体突变面板会破坏。这 由FGF调节的生化，分子和细胞过程 在体外和体内，将在肢体中分析 特定的发展事件是否被破坏。下游 FGF信号通路的组件将用于营救 中继FGF信号的突变表型和底物蛋白 被识别。