PI: Heberlein IBN-9604216 It is becoming increasingly obvious that the molecules that carry out important steps during the development of animals as diverse as fruitflies and mammals are quite similar, both in their structure as well as their function. This conservation has recently been extended to molecules that govern the development of the eye. For example, a fly gene (called eyeless) that plays a crucial role in building the eye has a human homolog known to be mutated in patients with Aniridia. Dr. Heberlein's group is studying the mechanisms and molecules that are required for the proper development of the eye in the fruitfly Drosophila. Of particular interest are two molecules, called hedgehog and decapentaplegic, which are needed for cells in the eye to communicate with each other so that the process of differentiation and assembly of the eye occurs in an orderly fashion. Dr. Heberlein's group has shown that, as the first photoreceptor cells differentiate in the retina, they begin expressing hedgehog. This hedgehog induces undifferentiated neighboring cells to activate the decapentaplegic gene and to differentiate as photoreceptors. These newly differentiated photoreceptors then begin to express hedgehog, which then induces their neighbors to undergo the same fate. This process repeats itself multiple times as the eye gradually develops into an orderly structure that is crucial for proper vision. Dr. Heberlein's group has also found that a fly mutant called Rough eye disrupts the normal development of the retina. When this occurs, the photoreceptor cells are disorganized, leading to a rough appearance of the eye's normally smooth surface. In this mutant, photoreceptors produce excessive amounts of hedgehog, and the process by which differentiation sweeps across the retina is disrupted. Dr. Heberlein plans to clone the gene disrupted by the Rough eye mutation and analyze the role of this gene during normal eye development. Results from this study will not only give us kn owledge about the intricate process of retinal development in Drosophila but probably reveal valuable information about eye development in a wide variety of organisms, including humans.