MOLECULAR GENETICS OF TOPOSOMES EUCARYOTES

真核生物拓扑体的分子遗传学

• 批准号: 3295754
• 负责人: HANS NOLL
• 金额: $ 18.61万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1988-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3295754
• 关键词: affinity chromatography; antibody; antibody neutralization test; biological information processing; blastema; cell adhesion; cell cell interaction; cell growth regulation; cell population study; chemical binding; complementary DNA; contact inhibition; cytogenetics; early embryonic stage; embryo /fetus cell /tissue; enzyme linked immunosorbent assay; eukaryote; gel electrophoresis; gene expression; genetic mapping; genetic regulation; immunoglobulins; immunoprecipitation; ligands; macromolecule; molecular cloning; molecular genetics; monoclonal antibody; nonmammalian vertebrate embryology; nucleic acid sequence; oligonucleotides; saltwater environment; surface antigens; tissue /cell culture

This project is concerned with the molecular basis of pattern formation in embryogenesis. The generation and maintenance of patterns in multicellular organisms requires the integration of four basic functions: (i) mechanical linkage between cells, (ii) positional guidance, (iii) control of DNA replication, and (iv) control of cell movement and shape. The project proposes that all of these functions are vested in one large multifunctional macromolecular assembly of which the toposome, a large oligomeric glycoprotein complex, is the cell surface component entrusted with mediating cell adhesion and expressing positional information. The central idea is that toposomes belongs to the general class of cell surface signal molecules that includes such well known glycoprotein complexes as the receptors for insulin, epidermal growth factor and receptors of the immune system. Toposomes share with these other receptors an extracellular binding domain recognizing a protein ligand, except that the ligand is the cognate portion of another toposome on a different cell. Toposomes are presumably bound to an integral membrane receptor that appears to be highly conserved and related to the fibronectin receptor. We further postulate that this receptor has a cytoplasmic signal generating domain, analogous to EPG and the family of membrane-bound proto-oncogenes, and a binding site for components of the cytoskeleton. The toposome concept will be tested by experiments that examine its predictions. Sequencing of the toposome genes that have been cloned for the sea urchin and Drosophila will have high priority. Other experiments are aimed at isolating peptides with the activity of the contact site and its characterization with monoclonal antibodies. These results will be combined with in situ labeling experiments of the developing embryo to deduce the positional code. involvement of toposomes in transduction of signals for DNA replication will be tested by blocking the contact site with ligands that restore DNA synthesis in dissociated cells of sea urchin embryos. Toposomes are thought to be key molecules in tumorigenesis because they would explain for the first time why in cancer loss of contact inhibition, positional guidance (leading to invasiveness) and cytoskeletal order are always linked.

这个项目是关于图案的分子基础