MOLECULAR PATTERNING OF LIMB MORPHOGENESIS

成人的四肢骨骼依赖于适当的生长、分支、 胚胎软骨的分割、迁移和融合。在这 应用程序中，我们检查了关键事件的发展控制 软骨形态发生--将单个软骨分割成两部分。 以雏鸡肢芽为实验模型，重点研究了 胚胎腓骨软骨分割的控制。此元素 显示了一个戏剧性的早期分段，深刻地影响了它的最终 骨骼表型。重要的是，这种正常的分段事件可以是 对实验操作感到不安，特别是通过将一个 前软骨前半部分和后半部分之间的屏障 肢芽(Hampe，1960)，造成严重的骨骼缺陷。去调查 软骨形态改变的机制及其可能的原因 对于肢体分割缺陷，我们建议重新审视这一实验 在细胞和分子水平上的操作，研究1) 前后信号在肢芽调控中的作用 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 软骨多层次发育的关键机制 形态发生将被确定。

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.