Lens epithelial cell differentiation

The differentiation of lens epithelial cells is an elaborate process that requires the coordination of many different cellular signaling pathways (Fig. 2). The process begins as cells in the anterior lens epithelium, which are committed to the lens lineage but are not differentiated, receive signals to enter the cell cycle. These signals require input from both integrins and growth factors and are mediated by Src family kinases and the ERK signaling pathway. The lens epithelial cells proliferate in the anterior aspects of the equatorial epithelium and before they begin to express characteristics specific to lens fiber cells, they withdraw from the cell cycle in the transition zone. This proliferation/differentiation decision is a crucial step for these cells and common to the regulation of many cell differentiation pathways. In the lens this transition requires the suppression of Src family kinase activity and the coordinated actions of molecules such as the CDK inhibitors p27 and p57, and Rb proteins. The ability of the lens epithelial cells to transition from proliferating to post-mitotic cells is correlated with their establishment of stable N-cadherin junctions. The initiation of the lens differentiation program requires the coordinated action of both integrins and growth factor receptors and their activation of downstream signaling pathways including the ERK MAP kinase pathway. Completion of the differentiation program of the lens fiber cell then involves molecules that regulate cell elongation, membrane stabilization, cell-cell communication and the establishment of cell transparency. While many of the aspects of lens epithelial cell differentiation are now understood, much more remains to be elucidated. Progress will be greatest if investigators expand their focus to include the notion that many different signaling pathways will be found to be involved in regulating the various incremental steps that lead a lens epithelial cell to become a fiber cell. Most important to this success will be the realization that creation of this exquisite tissue, the lens, is only possible through the cooperation of many different signaling effectors.