The objective of the proposed project is to continue our investigations on the mechanism of action and physiological significance of the neural cell adhesion molecule N-CAM during vertebrate embryogenesis. These studies are designed to define more fully the molecular structure of N-CAM and of cell-cell bonds, and to relate the chemical properties of N-CAM to its function in tissue morphogenesis and formation of nerve tracts. In addition to preparation of molecular reagents required for this work, the specific aims for the next five years include: 1) the description of structural features and molecular interactions that are required for neural cell-cell binding, 2) a comparison of N-CAM expression and structure in different tissues and developmental stages, 3) studies on the formation, structure and biological consequences of nerve bundling and branching, 4) a further evaluation of the role of N-CAM in muscle development and nerve-muscle interactions, and 5) the use of antibodies to characterize and perturb N-CAM during early stages of embryogenesis. These studies will involve experiments with embryos, tissues, cells, membrane vesicles, and purified cell surface molecules. Rabbit antisera and mouse monoclonal antibodies will be used extensively for the characterization of N-CAM, and for inhibition of its function in cultures and in vivo. Evaluation of the biological consequences of N-CAM mediated adhesion will involve phase, immunofluorescence and electron microscopy, combined with serial reconstructural computer graphics and techniques for labeling neuronal tracts. Previous work on N-CAM already indicates that this molecule is expressed during many phases of development, and is associated with a variety of tissues that undergo rapid remodeling. It is hoped that the proposed studies will lead to a more refined description of the molecular and cellular events associated with cell-cell adhesion, and consequently a more fundamental understanding of tissue formation during embryogenesis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD018369-04
Application #
3315405
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1983-12-01
Project End
1988-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Canger, Anthony K; Rutishauser, Urs (2004) Alteration of neural tissue structure by expression of polysialic acid induced by viral delivery of PST polysialyltransferase. Glycobiology 14:83-93
Petridis, Athanasios K; El-Maarouf, Abderrahman; Rutishauser, Urs (2004) Polysialic acid regulates cell contact-dependent neuronal differentiation of progenitor cells from the subventricular zone. Dev Dyn 230:675-84
El Maarouf, Abderrahman; Rutishauser, Urs (2003) Removal of polysialic acid induces aberrant pathways, synaptic vesicle distribution, and terminal arborization of retinotectal axons. J Comp Neurol 460:203-11
Glass, J D; Watanabe, M; Fedorkova, L et al. (2003) Dynamic regulation of polysialylated neural cell adhesion molecule in the suprachiasmatic nucleus. Neuroscience 117:203-11
Prosser, Rebecca A; Rutishauser, Urs; Ungers, Grace et al. (2003) Intrinsic role of polysialylated neural cell adhesion molecule in photic phase resetting of the Mammalian circadian clock. J Neurosci 23:652-8
Bruses, Juan L; Chauvet, Norbert; Rubio, Maria E et al. (2002) Polysialic acid and the formation of oculomotor synapses on chick ciliary neurons. J Comp Neurol 446:244-56
Fedorkova, Lenka; Rutishauser, Urs; Prosser, Rebecca et al. (2002) Removal of polysialic acid from the SCN potentiates nonphotic circadian phase resetting. Physiol Behav 77:361-9
Marx, M; Rutishauser, U; Bastmeyer, M (2001) Dual function of polysialic acid during zebrafish central nervous system development. Development 128:4949-58
Bruses, J L; Chauvet, N; Rutishauser, U (2001) Membrane lipid rafts are necessary for the maintenance of the (alpha)7 nicotinic acetylcholine receptor in somatic spines of ciliary neurons. J Neurosci 21:504-12
Murakami, S; Seki, T; Rutishauser, U et al. (2000) Enzymatic removal of polysialic acid from neural cell adhesion molecule perturbs the migration route of luteinizing hormone-releasing hormone neurons in the developing chick forebrain. J Comp Neurol 420:171-81

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