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Genetic Control of Limb Development

四肢发育的遗传控制

基本信息

批准号：
7616126
负责人：
Caroline N Dealy
金额：
$ 77.75万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-02-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7616126
关键词：
Genetic Control Limb Development

项目摘要

DESCRIPTION (provided by applicant): The objective of the Program is to study the molecular regulation of the outgrowth, patterning, and regeneration of the developing vertebrate limb. In Project 1, the hypothesis that the extracellular macromolecule hyaluronan (HA) facilitates the outgrowth, proliferation, and directed migration of limb mesenchymal cells in response to the apical ectodermal ridge (AER) will be investigated, as will the hypothesis that HA acts in concert with the EGFR/ErbB signaling network in the regulation of limb outgrowth and patterning. The role of HA in regulating the onset of limb cartilage differentiation will also be studied, as will its role in AER activity. In Project 2, the roles of the EGFR/ErbB family of tyrosine kinase receptors and ligands in the formation and function of the AER and in the signaling pathways that control limb patterning along the anteroposterior and dorsoventral axes will be investigated, as will role of EGFR/ErbB signaling in the programmed cell death involved in shaping limb contours. In Project 3, the cellular and molecular mechanisms that regulate digit tip regeneration in the embryonic mouse limb bud and the AER-dependent regeneration of the chick limb bud will be studied. In particular, the roles of directed cell migration and differential cell adhesion in the regeneration response will be investigated, as will the roles and relationships among Dlx genes, Msx genes, BMP signaling, FGFs, EGFR/ErbB signaling, and hyaluronan in the control of mammalian digit tip and chick limb bud regeneration. The Projects will be supported by an Administrative Core (Core A) that will manage the financial aspects of the research budgets.

描述(申请人提供)：该计划的目标是研究脊椎动物肢体发育过程中的生长、构型和再生的分子调控。在项目1中，将研究细胞外大分子透明质酸(HA)促进肢体间充质细胞在顶端外胚层脊(AER)反应中的生长、增殖和定向迁移的假说，以及HA与EGFR/ErbB信号网络在调节肢体突起和图案方面协同作用的假说。还将研究HA在调节肢体软骨分化开始中的作用，以及它在AER活性中的作用。在项目2中，将研究EGFR/ErbB家族酪氨酸激酶受体和配体在AER的形成和功能中的作用，以及在控制肢体前后和背腹轴上的肢体模式的信号通路中的作用，以及EGFR/ErbB信号在形成肢体轮廓的程序性细胞死亡中的作用。在项目3中，将研究调控小鼠胚胎肢芽指尖再生的细胞和分子机制，以及依赖AER的鸡肢芽再生。特别是，将研究定向细胞迁移和差异细胞黏附在再生反应中的作用，以及DLX基因、MSX基因、BMP信号、FGFs、EGFR/ErbB信号和透明质酸在控制哺乳动物指尖和鸡肢芽再生中的作用和关系。这些项目将得到一个行政核心(核心A)的支持，该核心将管理研究预算的财务方面。