MOLECULAR PATTERNING OF LIMB MORPHOGENESIS

肢体形态发生的分子模式

• 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
• 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

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.

成年人的四肢骨骼取决于正常的生长，分支， 胚胎软骨的分裂、迁移和融合。 在这 应用，我们研究了一个关键事件的发展控制， 软骨形态发生-单个软骨分割成两个。 以鸡肢芽为实验模型， 控制胚胎腓骨中的软骨分割。 此元素 显示了一个戏剧性的早期分割，深刻地影响了它的最终 骨骼表型 重要的是，这种正常的分割事件可以是 受到实验操作的干扰，特别是通过放置一个 前软骨前半部分和后半部分之间的屏障 肢芽（Hampe，1960），造成严重的骨骼缺损。 探讨 改变软骨模式的机制和可能的原因 肢体分割缺陷，我们建议重新审视这个实验 操纵在细胞和分子水平，调查1） 前后信号在控制肢芽中的作用 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 脊椎动物的肢芽 通过比较正常和异常的软骨 多层次的发展，软骨的关键机制 将鉴定形态发生。