The long term goal of this proposal is to understand the molecular and developmental biology of the mammalian photoreceptor cell. Using both 'Whole Tissue' Northern blots and topographical analysis of photoreceptor cell transcript levels by liquid hybridization, we observed that rhodopsin mRNA accumulates in distinct and reproducible topographic patterns across the retina. We propose to establish whether similar topographical patterns of gene expression exist for cone opsins as well as other genes of the phototransduction cycle including 48K protein, and subunits of transducin, cGMP phosphodiesterase, cGMP gated channel, and genes involved in the vitamin A cycle including interphotoreceptor retinol binding protein, cellular 11-cis retinaldehyde binding protein, and cellular retinol binding protein. The generality of such topographic gene expression will be assessed by similar analysis of primate and human retina as tissue becomes available. We also wish to understand how topographical patterns of development become established during fetal development. To this end, we will follow topography of expression for the above genes from the time of general transcriptional induction at 6 months fetal development to term at 9 months in the cow. Finally, towards understanding the mechanism regulating topographic expression, we will utilize an in vitro transcription system developed in our lab for photoreceptor genes to determine why some photoreceptor cells express higher levels of rhodopsin messenger than others.
| Timmers, A M; Fox, D A; He, L et al. (1999) Rod photoreceptor maturation does not vary with retinal eccentricity in mammalian retina. Curr Eye Res 18:393-402 |
| Timmers, A M; Wintjes, E T; Hauswirth, W W (1995) Fetal topography of bovine rhodopsin mRNA suggests retinotopographically determined gene expression. Invest Ophthalmol Vis Sci 36:2008-19 |
| van Ginkel, P R; Timmers, A M; Szel, A et al. (1995) Topographical regulation of cone and rod opsin genes: parallel, position dependent levels of transcription. Brain Res Dev Brain Res 89:146-9 |
| DesJardin, L E; Lockwood, M K; Hauswirth, W W (1995) Bovine opsin gene expression exhibits a late fetal to adult regulatory switch. J Neurosci Res 40:728-36 |
| DesJardin, L E; Timmers, A M; Hauswirth, W W (1993) Transcription of photoreceptor genes during fetal retinal development. Evidence for positive and negative regulation. J Biol Chem 268:6953-60 |
