MOLECULAR STUDIES OF FASCICLIN 2 IN NEURAL DEVELOPMENT

    Project: Research project

    Description

    The proposed research is a molecular investigation of growth cone
    pathfinding mediated by the fasciclin 2 (Fas2) protein, with the long-term
    objective of understanding neural specificity by defining the biochemical
    mechanisms for cell-cell recognition in the developing central nervous
    system (CNS). The experimental approach is to study the expression and
    function of Fas2 by application of molecular and genetic methods primarily
    in the fruit fly Drosophila melanogaster, and cellular and anatomical
    techniques mainly in the grasshopper, Schistocerca americana. Fasciclin 2
    is a cell surface glycoprotein isolated from grasshopper which is very
    similar in structure to vertebrate neural cell adhesion molecules (such as
    N-CAM, L1, contactin and myelin-associated glycoprotein), having 5
    immunoglobulin-type domains and 2 fibronectin-like regions. It is expressed
    at first on a single longitudinal axon bundle in the CNS, and antibodies
    against it disrupt the formation of this axon bundle by retarding or
    blocking the initial fasciculation of its constituent axons. The specific
    goals of my proposal are these: (a) isolation and characterization of Fas2
    cDNA and protein from Drosophila melanogaster; (b) isolation of the gene fo
    Fas2; and (c) isolation and characterization of Drosophila melanogaster
    which lack a functional Fas2 gene; and (d) determination of the biochemical
    mechanism of Fas2 action, including molecular structure-function studies on
    Fas2 in transfected cells and germ-line transformed Drosophila embryos. Al
    four specific aims will be approached initially by using the previously-
    characterized grasshopper Fas2 cDNA to isolate new Fas2 cDNA and genomic DN
    clones from Drosophila and grasshopper. Using standard techniques of
    molecular biology, these DNA fragments will be altered in specific ways and
    their function and expression tested after transfection into cell lines and
    into the Drosophila germ line. The discovery of Fas2 provides a unique
    opportunity to study a cell adhesion/recognition molecule using a potential
    ly powerful combination of molecular genetic, cell biological and anatomica
    methods in these model systems. The results from this project will help us
    understand how related molecules such as human N-CAM may function in brain
    development.
    StatusFinished
    Effective start/end date8/1/903/31/95

    Funding

    • National Institutes of Health
    • National Institutes of Health: $104,068.00
    • National Institutes of Health
    • National Institutes of Health: $124,602.00

    Fingerprint

    Grasshoppers
    Drosophila
    Axons
    Germ Cells
    Molecular Biology
    Contactins
    Complementary DNA
    Myelin-Associated Glycoprotein
    Fasciculation
    Drosophila Proteins
    Neural Cell Adhesion Molecules
    Transformed Cell Line
    Membrane Glycoproteins
    Cell Adhesion Molecules
    Molecular Structure
    Drosophila melanogaster
    Fibronectins
    Diptera
    Genes
    Transfection

    ASJC

    • Medicine(all)