The objectives of this investigator are to investigate the mechanism of action and biological significance of cell-cell adhesion molecules (CAMs) during development of the vertebrate embryo. The major focus of this work is the neural cell adhesion molecule (NCAM), which is a broadly distributed cell surface protein whose binding functions and unusual polysialic acid (PSA) moiety influence a wide variety of cell interactions. A multidisciplinary approach is proposed that includes analyses of the purified glycoprotein, membrane vesicles, cDNA transfected cells, and intact tissues from enzymatically or genetically altered embryos. Individual experiments focus on characterization of the functional domains of NCAM, on the regulated biosynthesis of PSA, as well as an analysis of the role of the NCAM polypeptide and PSA isoforms in a variety of well established developmental systems.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HD018369-14
Application #
2025083
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1983-12-01
Project End
1998-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
14
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Genetics
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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
Rafuse, V F; Polo-Parada, L; Landmesser, L T (2000) Structural and functional alterations of neuromuscular junctions in NCAM-deficient mice. J Neurosci 20:6529-39

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