Our research goal is to identify fundamental mechanisms governing the development of the vertebrate central nervous system through systematic genetic and molecular analyses. We concentrate our efforts on the neural retina, the photosensitive lining of the back of the eye. Like many regions of the brain, the anatomical organization, biochemical processes and gene expression patterns in the retina are conserved in virtually all vertebrate species. Our hope is that an understanding of the pathways that regulate gene expression and ultimately cellular differentiation in the neural retina will aid in the identification and management of genetic disorders affecting the visual system such as retinitis pigmentosa, macular degeneration and glaucoma.
As one model of vertebrate development, we utilize the zebrafish (Danio rerio), a small fresh water teleost that is easily adapted genetic studies. Currently underway in our laboratory is a systematic screen of larval and adult zebrafish to uncover mutations in genes regulating eye development and visual system function. We have recovered numerous classes of mutations including several that affect retinal lamination, photoreceptor differentiation and survival, or the differentiation and clarity of the crystalline lens. These mutations provide a valuable resource to genetically dissect the biochemical pathways involved in the the affected tissue as well as providing valuable models of genetic defects affecting human vision. The characterization of the existing mutations and the search for new mutations are continuing in the laboratory.
Our second major area of investigation hopes to unlock fundamental mechanisms governing the orderly patterning of cells in the retina. Similar to the well characterized mosaic patterning of the photoreceptors in Drosophila, we recently discovered a mosaic organization to the photoreceptors in the zebrafish. Making use of our ability to generate transgenic zebrafish, we described the novel arrangement using transgenic animals expressing a green fluorescent (eGFP) under the control of a rod specific promoter (Dev Biol, 2003). The expression of eGFP can be observed in living embryos due to their optical clarity and external fertilization in combination with recent advances in microscopy and analysis tools. We continue to develop alternative transgenic strategies to address specific questions of neural development and patterning.