REGULATION OF LIMB CHONDROGENESIS

发展中的肢体是研究机构的有用模型。 在发育过程中参与组织构图。这项建议 与导致差异化的过程有关 软骨元素在其适当的空间关系中的 发育中的鸟类和老鼠的肢体。通过嫁接研究 卵子和组织培养的研究、动力学和诱导性 我们将检查肢体外胚层的性质。外胚层 抑制软骨分化的衍生因子将是 特色化的。通过使用高密度培养系统，其中 软骨形成的发生，通过特定的相互作用的机制 将对间充质细胞促进软骨形成进行分析。 将特别关注细胞外基质 肌动蛋白细胞骨架的受体和组织变化 在软骨形成的启动过程中。研究也将是 与软骨前细胞外基质的性质有关 分子及其在软骨形成中的作用。胰岛素样物质的作用 生长因子I在软骨形成中的作用及在修复软骨缺陷中的作用 将研究耳垂小鼠突变模型中的软骨形成 利用IGF-I封闭抗体和分子生物学技术在细胞培养中的应用 探测器。最后，细胞形状改变的机制 调控软骨特异基因的表达将是 检查过了。我们将特别关注翻译层面 调节各种胶原蛋白的合成。

The developing limb is a useful model for studies on the mechanisms involved in tissue patterning during development. This proposal is concerned with the processes that lead to the differentiation of cartilage elements in their proper spacial relationships in the developing avian and mouse limb. By means of grafting studies in ovo and tissue culture studies, the dynamics and inductive properties of the limb ectoderm will be examined. An ectodermally derived factor that inhibits cartilage differentiation will be characterized. By use of a high density culture system in which chondrogenesis occurs, the mechanism by which specific interactions between mesenchymal cells promote chondrogenesis will be analyzed. Particular attention will be placed on extracellular matrix receptors and changes in the organization of the actin cytoskeleton in the initiation of chondrogenesis. Studies will also be concerned with the nature of a precartilage extracellular matrix molecule and its role in chondrogenesis. The role of insulin-like growth factor I in chondrogenesis and in mediating defects in chondrogenesis in the droopy ear mouse mutant model will be studied in cell cultures by use of blocking antibody to IGF-I and molecular probes. Finally, the mechanism by which cell shape changes modulate the expression of cartilage specific genes will be examined. Particular attention will be placed on translation level regulation of the synthesis of various collagen types.