Forkhead Box Protein P1 Is Dispensable for Retina but Essential for Lens Development.

Abstract

Forkhead box protein P1 (Foxp1) is a transcriptional repressor expressed in many tissues. We identified Foxp1 as a highly expressed gene in retinal progenitor cells and investigated its roles during eye development. Mouse eyes with Foxp1 gain- or loss-of-function were established in vitro and in vivo. Foxp1 overexpression in retinal progenitor cells resulted in reduced rod and increased cone photoreceptors. However, retina-specific knockout of Foxp1 was not associated with retinal differentiation abnormalities. Foxp1 was highly expressed in the lens during early development, and continued to be expressed in epithelial and cortical fiber cells until adulthood. At birth, analyses of Foxp1 lens-specific knockout (Foxp1-L-CKO) mice showed no gross morphologic changes in germinal or central epithelial cell compared to the controls. However, the numbers of proliferating and apoptotic cells were significantly increased in Foxp1-L-CKO mice. In addition, clear Y-structures were not observed in either the posterior or anterior sutures of the Foxp1-L-CKO lenses. Mature lenses of Foxp1-L-CKO mice were small and opaque. The fiber cell structure in the core and the cortical fiber cell columns were disturbed in Foxp1-L-CKO mice at postnatal day 14, potentially accounting for the opacity. In addition, epithelial cells were not aligned into columns along the transition zone in Foxp1-L-CKO mice. Taken together, these results suggest that Foxp1 has a role during lens growth in epithelial and differentiating fiber cells. Loss of Foxp1 results in loss of suture and fiber cell alignment, which eventually causes lens opacity, suggesting that Foxp1 has a key role in establishing cortical lens architecture.