MOLECULAR BASIS OF NORMAL AND MUTANT LIMB DEVELOPMENT

本研究的总体目标是研究 软骨基质的大分子，并了解这些 大分子相互作用影响形态发生过程中， 胚胎肢体的发育。具体来说，我们将调查链接 蛋白（LP）和软骨基质蛋白（CMP）在肢体形态发生过程中的作用。 在软骨中，LP与聚集蛋白聚糖和透明质酸形成三元复合物 (HA)并稳定聚集蛋白聚糖-HA相互作用。CMP是一种分子 有丝分裂后软骨细胞的标志物，与胶原蛋白相关 软骨中的纤维。这两种分子有着非常不同的 表情LP普遍表达，CMP表达普遍。 仅限于软骨。在长骨的生长板中，LP基因 在增殖区和成熟区都有转录，而 CMP基因的转录仅发生在成熟区。我们 将使用转基因方法来测试几个假设， 我们的生化数据。所使用的转基因方法是 复制能力禽逆转录病毒与转基因将 传递到培养的软骨细胞和完整胚胎中。的作用 CMP将在软骨细胞增殖、基质建立方面进行评价 和骨骼发育。LP在建立和 维持细胞外基质的完整性将是 研究了

The overall goal of the research is study the interactions between macromolecules of the cartilaginous matrix and to understand how these macromolecular interactions influence morphogenetic processes during the development of the embryonic limb. Specifically, we will investigate link protein (LP) and cartilage matrix protein (CMP) during limb morphogenesis. In cartilage, LP forms a ternary complex with aggrecan and hyaluronic acid (HA) and stabilizes the aggrecan-HA interactions. CMP is a molecular marker for post-mitotic chondrotytes and associates with the collagen fibril in cartilage. These two molecules have very different patterns of expression. LP is ubiquitously expressed and the expression of CMP is restricted to cartilage. In the growth plate of the long bones the LP gene is transcribed in both the zones of proliferation and maturation, whereas transcription of the CMP gene occurs only in the zone of maturation. We will use transgenic approaches to test several hypotheses that are based on our biochemical data. The transgenic approach to be used is the replication competent avian retrovirus with which transgenes will be delivered to chondrocytes in culture and in the intact embryo. The role of CMP will be evaluated on chondrocyte proliferation, matrix establishment and skeletal development. The role of LP in the establishment and maintenance of the integrity of the extracellular matrix will be investigated.