Biochemical and physiological processes in multicellular animals require the coordinated interactions of many cells. Maintenance of these cell-cell associations of the specific cell junctions which arise from them is the basis of tissue function. The purpose of this Project is to determine the role of one specific embryonic cell surface constituent in the control of retina cell-cell recognition, and in the development of neuronal connections. We have purified this constituent, the neural retina cognin; it is a glycoprotein which enhances the reaggregation of dissociated chick and mouse neural retina cells in vitro. Scanning electron microscopy localization of the cell surface cognin suggests that its distribution in the retina, on differnt retina cell types, and the changes in such a distribution during development, may be significant in elucidating the role of cognin in vivo. We propose, first, to identify other cell surface molecules which must interact with cognin, and to thereby reconstruct the mechanism of cell-cell recognition. This will be done by affinity chromatography to identify molecules which bind cognin, and by studying a simple model system, the in vitro interaction of membranevesicles prepared from retina cells. We will also utilize the available polydeterminant antibody to cognin to determine the localization of cognin in vivo. This will be compared to the distribution of cognin on cell types isolated from the retina by density gradient fractionation in order to determine the possible role of cognin in two critical morphogenetic phases of retina development. These are; the early inductive interactions between retina and other optic area tissues, and the development of the stratified architecture of the mature retina. Finally, we propose to test a specific hypothesis that cognin plays a role in the development of synapses later retinogenesis.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY004461-03A2
Application #
3258893
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-09-30
Project End
1990-09-29
Budget Start
1987-09-30
Budget End
1988-09-29
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Arts and Sciences
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Holdengreber, V; Ren, Y; Ben-Shaul, Y et al. (1998) Co-localization of the insulin receptor, jun protein and choline acetyltransferase in embryonic chick retina. Exp Eye Res 66:307-13
Ren, Y; Holdengreber, V; Ben-Shaul, Y et al. (1997) Causal role for jun protein in the stimulation of choline acetyltransferase by insulin in embryonic chick retina. Biochem Biophys Res Commun 232:788-93
Shah, B H; Hausman, R E (1993) Effect of insulin on GABAergic development in the embryonic chick retina. Brain Res Dev Brain Res 72:151-8
Krishna Rao, A S; Hausman, R E (1993) cDNA for R-cognin: homology with a multifunctional protein. Proc Natl Acad Sci U S A 90:2950-4
Shah, B H; Hausman, R E (1993) Effects of cell signaling on the development of GABA receptors in chick retina neurons. Neurochem Res 18:957-64
Sagar, G D; Rao, A S; Ren, Y et al. (1992) The cell recognition molecule, cognin, mediates choline acetyltransferase activity in embryonic chick retina. Brain Res 585:63-70
Shah, B H; Rao, A S; Hausman, R E (1992) Role of the cell recognition molecule, cognin, in GABAergic differentiation in chick retina. Brain Res 589:268-74
Hausman, R E; Sagar, G D; Shah, B H (1991) Initial cholinergic differentiation in embryonic chick retina is responsive to insulin and cell-cell interactions. Brain Res Dev Brain Res 59:31-7
Dobi, E T; Naya, F J; Hausman, R E (1988) Distribution of R-cognin and choline acetyltransferase in the ganglion cell layer of developing chick neural retina. Cell Differ 22:115-23
Troccoli, N M; Hausman, R E (1988) Retina cognin does not bind to itself during membrane interaction in vitro. Cell Differ 22:225-31

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