MOLECULAR GENETICS OF TOPOSOMES EUCARYOTES
真核生物拓扑体的分子遗传学
基本信息
- 批准号:3295757
- 负责人:
- 金额:$ 15.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1989
- 资助国家:美国
- 起止时间:1989-01-01 至 1993-12-31
- 项目状态:已结题
- 来源:
- 关键词:DNA replication Drosophilidae affinity chromatography antibody antibody neutralization test binding proteins 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 embryogenesis enzyme linked immunosorbent assay eukaryote gel electrophoresis gene expression genetic mapping genetic regulation glycoproteins immunoglobulins immunoprecipitation laboratory mouse laboratory rabbit ligands macromolecule membrane proteins molecular cloning molecular genetics monoclonal antibody nonmammalian vertebrate embryology nucleic acid hybridization nucleic acid probes nucleic acid sequence oligonucleotides protein biosynthesis protein sequence receptor saltwater environment sea urchins surface antigens tissue /cell culture
项目摘要
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
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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