MOLECULAR GENETICS OF BASEMENT MEMBRANES IN C ELEGANS

基底膜是特化的细胞外基质结构， 在所有后生动物中，被认为在几个重要的功能中起作用， 发育过程，包括;细胞粘附，细胞迁移，细胞 分化和形态发生。 基底膜也被认为 参与某些病理状况，如肿瘤转移， 伤口愈合，皮肤起泡疾病，以及某些形式的 肾炎 关于基底膜功能的知识 主要来源于对纯化的基底膜成分的研究， 已经进行了基底膜功能的遗传研究。 之一 基底膜中最丰富和普遍存在的成分是 基底膜特异性IV型胶原。 最近确定的 基因突变，编码两个IV型胶原蛋白链， 线虫秀丽隐杆线虫提供了第一个机会， 基底膜功能分析。 本申请的目的是 对基底膜结构进行遗传和分子分析 并在C.优雅 强大的基因和分子分析 这在C中是可能的。优雅的，和它简单的，定义明确的解剖学，使 它是研究地下室结构和功能的一个很好的系统 膜。 IV型胶原基因的多个独立突变 以及它们对C.雅丽根将 可以通过显微镜和分子分析的组合来确定。 的 由这些突变引起的核苷酸和氨基酸序列改变 将被确定，并将提供价值信息， IV型胶原分子的功能重要区域。 遗传 将鉴定与IV型胶原蛋白基因相互作用的基因座， 因为它们可能编码其他基底膜成分。 等 相互作用基因座可编码已知的基底膜成分，例如 层粘连蛋白、巢蛋白或硫酸乙酰肝素蛋白聚糖核心蛋白，或 可以编码以前未识别的基底膜成分。 相互作用基因座的突变分析也将确定 与基因座发生物理相互作用的不同蛋白质也将定义 不同蛋白质内的区域， 膜。 对C. elegans将提供一个 更好地了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.