The objectives of this proposal are to understand the role of a specific group of cell surface glycolipids and glycoproteins in cell-cell interactions in olfactory receptor cells. It is designed to test the hypothesis that cell surface carbohydrate antigens interact with ligands on adjacent cell surfaces or on extracellular structures resulting in functionally relevant cellular interactions in the developing, mature and regenerating olfactory system. Three glycoconjugates were recently described which are specifically expressed on subsets of olfactory sensory neurons and their axons. Because of their unique distribution, all three glycoconjugates are candidate cell-cell interaction molecules which may participate in the establishment and maintenance of a functional olfactory system. Two of these molecules in particular may participate in mechanisms which guide olfactory axons to their targets in the olfactory bulb. A third glycoconjugate is expressed on olfactory neurons during an intermediate stage of their maturation and is likely to be relevant for studies of new olfactory connections in adult animals. In the proposed studies, the carbohydrate structures will be chemically characterized using chromatographic and mass spectrometric techniques. Carbohydrate binding proteins which are believed to participate in these cellular interaction will also be identified and chemically characterized. The detailed localization of these glycoconjugates and binding proteins will be analyzed during embryonic and postnatal development using immunocytochemical and electron microscopic techniques. In addition regeneration studies will be conducted to analyze the expression of the glycoconjugates during maturation of olfactory neurons. Glycosyltransferase studies will also be performed in order to understand the regional and age-related differences in expression of maturation-dependent glycoconjugates. This proposal represents a multifaceted approach, combining chemical, cellular, and anatomical analyses to define the role of a group of unique molecules to the olfactory system. These studies will provide insight into the molecular and cellular basis of olfactory structure and function and may illuminate mechanisms of pathogenesis in degenerative sensory disorders.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Neurology C Study Section (NEUC)
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Eunice Kennedy Shriver Center Mtl Retardatn
United States
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Henion, Timothy R; Schwarting, Gerald A (2014) N-linked polylactosamine glycan synthesis is regulated by co-expression of ?3GnT2 and GCNT2. J Cell Physiol 229:471-8
Henion, Timothy R; Madany, Pasil A; Faden, Ashley A et al. (2013) ?3GnT2 null mice exhibit defective accessory olfactory bulb innervation. Mol Cell Neurosci 52:73-86
Knott, Thomas K; Madany, Pasil A; Faden, Ashley A et al. (2012) Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance. Neural Dev 7:17
Schwarting, Gerald A; Henion, Timothy R (2011) Regulation and function of axon guidance and adhesion molecules during olfactory map formation. J Cell Biochem 112:2663-71
Henion, Timothy R; Faden, Ashley A; Knott, Thomas K et al. (2011) ?3GnT2 maintains adenylyl cyclase-3 signaling and axon guidance molecule expression in the olfactory epithelium. J Neurosci 31:6576-86
Schwarting, Gerald A; Henion, Timothy R (2008) Olfactory axon guidance: the modified rules. J Neurosci Res 86:11-7
Schwarting, Gerald A; Gridley, Thomas; Henion, Timothy R (2007) Notch1 expression and ligand interactions in progenitor cells of the mouse olfactory epithelium. J Mol Histol 38:543-53
Henion, Timothy R; Schwarting, Gerald A (2007) Patterning the developing and regenerating olfactory system. J Cell Physiol 210:290-7
Schwarting, Gerald A; Henion, Timothy R; Nugent, J David et al. (2006) Stromal cell-derived factor-1 (chemokine C-X-C motif ligand 12) and chemokine C-X-C motif receptor 4 are required for migration of gonadotropin-releasing hormone neurons to the forebrain. J Neurosci 26:6834-40
Henion, Timothy R; Raitcheva, Denitza; Grosholz, Robert et al. (2005) Beta1,3-N-acetylglucosaminyltransferase 1 glycosylation is required for axon pathfinding by olfactory sensory neurons. J Neurosci 25:1894-903

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