The overall goal of the proposed work is to identify and understand the functions and interactions of genes essential for vertebrate retinal development and maintenance. Zebrafish will be utilized as the animal model as it presents a unique combination of characteristics amiable to experimentation; in particular, as a representative species for vertebrate mutagenesis. The young mutation, which lacks lamination and morphological differentiation in the retina, will be characterized for the expression of molecules that mark stages of differentiation in order to test the hypothesis that lamination is necessary for establishing microenvironments within the retina that are critical for proper cell type specification. Additional lamination, as well as other ocular morphogenetic mutations will be screened for, isolated, and characterized. Double mutational analysis with young will be performed to test for genetic or epigenetic interactions and to establish hierarchical relationships between essential genes for retinal lamination and specification. These studies will forward our understanding of normal retinal development and establish candidate genes or functions for those already linked with pathogenesis in human ocular diseases.
