MOLECULAR PATTERNING OF LIMB MORPHOGENESIS

肢体形态发生的分子模式

基本信息

批准号：
2519105
负责人：
ELIZABETH E LECLAIR
金额：
$ 3.02万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-10-06 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/2519105
关键词：
Retroviridae biological signal transduction bone morphogenetic proteins cartilage development cell cell interaction cell migration chick embryo extracellular matrix gene expression histogenesis histology limb bone limbs

项目摘要

The adult limb skeleton depends on the proper growth, branching, segmentation, migration and fusion of embryonic cartilages. In this application, we examine the developmental control of a key event in cartilage morphogenesis-the segmentation of a single cartilage into two. Using the chick limb bud as an experimental model, we focus on the control of cartilage segmentation in the embryonic fibula. This element shows a dramatic early segmentation that profoundly affects its final skeletal phenotype. Importantly, this normal segmentation event can be perturbed by experimental manipulation, specifically by placing a barrier between anterior and posterior halves of the pre-cartilaginous limb bud (Hampe, 1960), creating major skeletal defect. To investigate the mechanisms of altered cartilage patterning and the possible causes of limb segmentation defects, we propose to revisit this experimental manipulation at the cellular and molecular level, investigating 1) the role of antero-posterior signaling in the control of limb bud morphogenesis, 2) the importance of cell-cell and cell-matrix interactions during cartilage segmentations, migrations, and fusions, and 3) molecular pathways of cartilage morphogenesis in the early vertebrate limb bud. By comparing normal and abnormal cartilage development at multiple levels, key mechanisms of cartilage morphogenesis will be identified.

成年肢体骨骼取决于适当的生长，分支，胚胎软骨的分割，迁移和融合。在这个应用，我们检查了关键事件的发展控制软骨形态发生 - 将单个软骨分割为两个。使用小鸡肢体作为实验模型，我们专注于控制胚胎腓骨中软骨分割的控制。这个元素显示出戏剧性的早期细分，深刻影响其最终骨骼表型。重要的是，这个正常的分割事件可以是受到实验操作的扰动，特别是通过放置前半部分的前半部分之间的障碍物肢体芽（Hampe，1960年），造成了主要的骨骼缺陷。调查改变软骨模式的机制和可能的原因肢体分割缺陷，我们建议重新审视此实验在细胞和分子水平上操作，研究1）前后信号传导在肢体芽控制中的作用形态发生，2）细胞细胞和细胞基质的重要性软骨分割，迁移和融合过程中的相互作用， 3）早期软骨形态发生的分子途径脊椎动物肢体芽。通过比较正常和异常软骨多个级别的开发，软骨的关键机制形态发生将被鉴定。