IBN 9602075 Pamela Raymond, PI Development of an embryo into a mature organism is a process in which orderly structures arise out of initially unorganized masses of cells, much like a house is built from a pile of crude lumber. Groups of cells, especially those that become the neurons of the brain, adopt unique and specialized identities, in a process developmental biologists call "differentiation". Differentiated cells of the same type are not clumped together helter-skelter, but are often positioned in a precise arrangement. For example, cone photoreceptors, which constitute a sheet of light-sensitive neurons in the retina of the eye, come in several varieties, distinct in that they express a specific visual pigment which is maximally sensitive to light of a certain color (red, green, blue or, in some animals, ultraviolet). In some vertebrates, such as fish, the cones are arranged in a regular, repeating lattice or mosaic array. The developmental mechanisms that build the lattice, i.e., that control the spacing and determine the fate of the presumptive cone photoreceptor cells, are not well understood. Most developmental biologists agree, however, that immature, differentiating cells often send signals to their neighbors instructing them what, or what not, to become. To begin to understand this process, the earliest stages in the differentiation of the cone mosaic in the fish embryo are being studied. Fish are an advantageous choice for this work, since at early developmental stages the embryo is small (about 1 mm in diameter) and transparent. Molecular markers are being used to identify the cone types by the specific visual pigment that they express -- red, green, blue or ultraviolet, and to distinguish them from the other major class of photoreceptors, called rods. The hypothesis under investigation is that precocious rod photoreceptors are the "founders" of the mosaic array. They establish a blueprint of the repeating pattern, and then through specific signaling mechanisms (as yet unide ntified), they induce differentiation and patterning of the array of red, green, blue and ultraviolet cones. These experiments will provide new information about the way cells communicate with each other during development.