Frizzled–5 Signaling During Mouse Eye Development

Abstract

Purpose: : Wnts are secreted glycoproteins that bind to Frizzled transmembrane receptors and regulate multiple developmental processes such as embryonic patterning, cell polarity, cell fate determination and proliferation. Recently, Wnt/Frizzled signalling has been shown to regulate different aspect of eye development in vertebrates. Since Frizzled–5 (Fz) expression is largely restricted to the mouse optic vesicle, our goal was to analyze the function of Fz5 during early eye development in mammals.

Methods: : We determined the expression of Fz5 mRNA during embryonic eye development in detail. Mouse embryos with a targeted deletion of Fz5 were analyzed for changes in BrDU incorporation, cell death and eye–specific gene expression.

Results: : Fz5 is expressed in retinal progenitors throughout embryonic development. Without Fz5, eye morphogenesis is severely disrupted; invagination of the optic vesicle does not occur and lens formation is arrested at the placode stage. The mutant optic vesicle is small and proliferation in the neural retina is decreased. In addition, the neural retina–specific marker FGF15 is downregulated and the lens–specific gene FoxE3 is absent in mutant optic vesicles.

Conclusions: : Our data suggests that Fz5 is critical for retinal proliferation and optic cup morphogenesis in the mammalian eye. Furthermore, Fz5 is likely required for the production of a retina–derived signal to promote lens development. Thus, Fz5 is an important regulator of early eye development in the rodents.

Keywords: retinal development • receptors • gene/expression