Figure 8.

A model for the coordination of cell cycle withdrawal and lens fiber differentiation by FGF signaling. Prox1 is required for the increased expression of p27^kip1 and p57^kip2 that mediates the entry of lens fiber cells into G0. Deficient FGF receptor signaling led to reduced expression of Prox1 and decreased expression of p27^kip1 and p57^kip2, resulting in the abnormal proliferation of cells that would normally form lens fibers. The transcription factor c-Maf promotes the expression of α-, β- and γ-crystallins and fiber cell elongation. FGF signaling deficiency led to decreased crystallin gene expression and failure of fiber cell elongation. FGF signaling is also required for the decrease in E-cadherin expression that normally accompanies fiber cell differentiation. Finally, increased apoptosis in the MLR10-mutant lenses suggests that FGF signaling is required for lens epithelial cell survival.