Our work has focused on three aspects of how lens differentiation is controlled at the molecular level. First, our work led to the understanding that the tumor suppressor protein pRb is essential for lens cells to withdraw from the cell cycle and differentiation, in part through its regulation of the activity of E2F transcription factors. The pRB family of proteins also appears to be essential for maintaining normal growth rates in the less differentiated, proliferating cells of the lens. More recently our studies have identified a new family of tumor suppressors, that of the discs-large family, DLG, as also being important for regulating normal cell growth and differentiation in the lens. Second, our studies addressed the mechanism of how lens cells eliminate their organelles, which occurs normally as lens cells differentiate. We now understand that certain members of the caspase family of proteases, the proteases that mediate apoptotic responses, are involved in regulating organelle loss. Finally, the FGF signaling pathways appears to be a regulator of multiple stages of lens cell differentiation and survival. Two areas of our current and future work are: (1) further elucidate the mechanisms through which pRB and DLG families of tumor suppressors control growth and differentiation in less differentiated, proliferating cells as well as in the differentiating cells of the lens; and (2) to identify the molecular pathway including caspases and DLG that regulate organelle loss in the lens and the relationship of this pathway to apoptosis. From our work, we hope to learn more about the mechanisms that regulate normal eye development and how dysregulation of these mechanisms can lead to ocular disorders such as cataracts, retinal degeneration and tumor formation.