The long term goal of this proposal is to understand the molecular and developmental biology of the mammalian photoreceptor cell. The timing and coordination of visual gene products expressed during mammalian fetal development is only fragmentarily understood. Even less is known concerning protein and nucleic-acid elements regulating such gene expression. This proposal focuses on a molecular understanding of the developmentally regulated expression of two photoreceptor cell specific genes, rhodopsin and interphotoreceptor binding protein (IRBP). Preliminary results in fetal bovine retina demonstrate that rhodopsin and IRBP mRNAs and protein are simultaneously induced 5 to 50-fold at 6 months gestation. This suggests that developmentally regulated retinal genes may be under common transcriptional control. Therefore, we propose to test the hypothesis that coordinately expressed, developmentally regulated photoreceptor genes contain common DNA transcriptional elements responsive to common regulatory proteins. Cis-DNA elements and trans-acting protein elements responsible for coordinating transcriptional control will be identified for each gene using an in vitro transcription system from both adult and fetal bovine retinal nuclei. In later years, this analysis will be extended to other photoreceptor cell-specific genes. This will lead to a clearer picture of photoreceptor development at the molecular level and should help form a basis for eventually tracing genetic defects in the mammalian retina to their molecular source.
Showing the most recent 10 out of 18 publications
