A growing body of work suggests that retinal cells carry positional markers. These markers serve to distinguish cells in different regions of the retina from one another, and they appear to be important in mediating specific cell-cell interactions. Although there is strong evidence for functional differences in the cells on the nasal and temporal sides of the developing retina, there is limited knowledge of the molecular diversity that underlies these differences. The goal of this project is to identify molecules asymmetrically expressed in the nasal-temporal axis of the developing retina and to determine the function of these molecules. The project is divided into four specific aims.First, TRAP, a molecule expressed by most ganglion cells on the temporal side of the retina and by few ganglion cells on the nasal side, will be characterized in more detail. This will involve cloning the gene for TRAP from a cDNA library, sequencing the gene, and developing antibodies to the protein for use in analyzing the function of TRAP. Second, three complementary approaches will be used to identify other molecules expressed asymmetrically between the nasal and temporal sides of the developing retina. These approaches include the use of monoclonal antibodies, cDNA cloning by subtractive hybridization, and lectin blots. As molecules are discovered, they will be characterized as described for TRAP. Third, anatomical differences between the nasal and temporal sides of the retina will be identified.This information will be used to develop in vivo assays to study the function of side-specific molecules and will allow specific patterns of axon growth to be correlated with the distribution of asymmetrically distributed molecules. Fourth, the function of molecules asymmetrically expressed in the developing retina will be examined. This will involve perturbing the function of these molecules with antibodies in vivo and in vitro. Preliminary studies will also evaluate techniques for introducing genes to alter the expression of specific molecules.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY005371-08
Application #
3260410
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1983-09-01
Project End
1995-09-29
Budget Start
1992-09-30
Budget End
1993-09-29
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Wu, H H; Williams, C V; McLoon, S C (1994) Involvement of nitric oxide in the elimination of a transient retinotectal projection in development. Science 265:1593-6
Williams, C V; Nordquist, D; McLoon, S C (1994) Correlation of nitric oxide synthase expression with changing patterns of axonal projections in the developing visual system. J Neurosci 14:1746-55
Williams, C V; Stechmann, C L; McLoon, S C (1992) Subtractive immunization techniques for the production of monoclonal antibodies to rare antigens. Biotechniques 12:842-7
Williams, C V; McLoon, S C (1991) Elimination of the transient ipsilateral retinotectal projection is not solely achieved by cell death in the developing chick. J Neurosci 11:445-53
McLoon, S C (1991) A monoclonal antibody that distinguishes between temporal and nasal retinal axons. J Neurosci 11:1470-7
Nordquist, D; McLoon, S C (1991) Morphological patterns in the developing vertebrate retina. Anat Embryol (Berl) 184:433-40
McLoon, S C; Barnes, R B (1989) Early differentiation of retinal ganglion cells: an axonal protein expressed by premigratory and migrating retinal ganglion cells. J Neurosci 9:1424-32
McLoon, S C; McLoon, L K; Palm, S L et al. (1988) Transient expression of laminin in the optic nerve of the developing rat. J Neurosci 8:1981-90
Rogers, S L; Edson, K J; Letourneau, P C et al. (1986) Distribution of laminin in the developing peripheral nervous system of the chick. Dev Biol 113:429-35
McLoon, S C (1986) Response of astrocytes in the visual system to Wallerian degeneration: an immunohistochemical analysis of laminin and glial fibrillary acidic protein (GFAP). Exp Neurol 91:613-21

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