MOLECULAR GENETICS OF BASEMENT MEMBRANES IN C ELEGANS

基底膜是一种特殊的细胞外基质结构 在所有后生动物中，它们被认为在几个重要的 发育过程，包括：细胞黏附、细胞迁移、细胞 分化和形态发生。基底膜也被认为是 与某些病理情况有关，如肿瘤转移， 伤口愈合，皮肤起泡疾病，以及某些形式的 肾炎。对基底膜功能的认识已经被 主要来源于对纯化的基底膜成分的研究，NO 基底膜功能的遗传学研究已经展开。其中之一 基底膜最丰富和最普遍的成分是 基底膜特异性IV型胶原。最近发现的 编码两个IV型胶原链的基因突变 线虫秀丽线虫提供了第一次遗传机会 基底膜功能分析。此应用程序的目标是 对基底膜结构进行遗传学和分子分析 并在线虫中发挥作用。强大的遗传和分子分析 在线虫中可能发生的事情，以及它简单、明确的解剖结构，使 它是研究地下室结构和功能的优秀系统 膜。IV型胶原基因的多个独立突变 以及它们对线虫发展的影响将 由显微分析和分子分析相结合来确定。这个 由这些突变引起的核苷酸和氨基酸序列改变 将被确定，并将为定义 IV型胶原分子的重要功能区域。遗传 与IV型胶原基因相互作用的基因座将被识别， 因为它们可能编码其他基底膜成分。是这样的 相互作用的基因座可以编码已知的基底膜成分，例如 层粘连蛋白、粘连蛋白或硫酸乙酰肝素蛋白多糖核心蛋白，或 可以编码以前未知的基底膜成分。 对相互作用基因座的突变分析也将定义 物理上相互作用的基因座的不同蛋白质也将定义 不同蛋白质中相互作用形成基底物的区域 膜。对线虫的遗传分析将提供一种 更好地理解地下室的结构和功能 膜。

Basement membranes are specialized extracellular matrix structures, found in all metazoans, that are believed to function in several important developmental processes, including; cell adhesion, cell migration, cell differentiation, and morphogenesis. Basement membranes are also thought to be involved in certain pathologic conditions, such as tumor metastasis, wound healing, blistering diseases of the skin, and certain forms of nephritis. Knowledge of the functions of basement membranes has been derived primarily from studies of purified basement membrane components, no genetic studies of basement membrane function have been performed. One of the most abundant and ubiquitous components of basement membranes is the basement membrane-specific type IV collagen. The recent identification of mutations in the genes that encode the two type IV collagen chains in the nematode Caenorhabditis elegans provides the first opportunity for genetic analyses of basement membrane functions. The aim of this application is to pursue both genetic and molecular analyses of basement membrane structure and function in C. elegans. The powerful genetic and molecular analyses that are possible in C. elegans, and its simple, well defined anatomy, make it an excellent system for studying the structure and functions of basement membranes. Multiple independent mutations in the type IV collagen genes will be generated and their effects on the development of C. elegans will be determined by a combination of microscopic and molecular analyses. the nucleotide and amino acid sequence alterations caused by these mutations will be determined and will provide value information towards defining functionally important regions of the type IV collagen molecule. Genetic loci that interact with the type IV collagen genes will be identified, since they are likely to encode other basement membrane components. Such interacting loci may encode known basement membrane components, such as laminin, entactin, or the heparan sulfate proteoglycan core protein, or could encode previously unidentified components of basement membranes. Mutational analyses of interacting loci will also define the regions within different proteins that physically interact loci will also define the regions within different proteins that physically interact to form basement membranes. The genetic analyses possible in C. elegans will provide a better understanding of both the structure and functions of basement membranes.