The overall objectives of this project are to investigate the mechanism of action and biological significance of cell-cell adhesion molecules (CAMs) during development. The major focus of this work is the neural cell adhesion molecule (NCAM), which is a broadly distributed cell surface protein believed to influence a wide variety of cell interactions. The approach involves of purified cell surface glycoproteins, membrane vesicles, cultured cells and explants, and intact chicken embryos. Studies focus on characterization of the structure of NCAM and of cell-cell bonds involving this molecule, as well as attempts to relate natural or induced variations in the expression or structural form of NCAM and other CAMs to changes in tissue structure. The following specific aims are proposed: 1. Development and characterize reagents required to study NCAM both in this and other laboratories. 2. Identify the molecular interactions involved in formation of an NCAM-mediated cell-cell bond. 3. Test the hypothesis that NCAM and other adhesion molecules in neurite outgrowth and fasciculation. 5. Develop a model cell culture system for study of CAMs, utilizing neuroblastoma-sensory ganglion neuron hybrids. 6. Continue the use of adhesion-perturbing antibodies and enzymes to relate chemical and in vitro observation to the in vivo development of tissues.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Cellular Biology and Physiology Subcommittee 1 (CBY)
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Case Western Reserve University
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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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