Abstract
Abstract: :
Purpose: The information about the role of Wnt signaling pathways in eye development is very limited. We have shown that 13 out of 19 chicken Wnt genes are expressed in the anterior part of the eye during early stages of development. Six of them are expressed in the lens and likely regulate differentiation of adjacent anterior eye tissues. This study was aimed to determine the specific phases in early differentiation of the anterior segment of the eye that are regulated by Wnt signaling. Methods: To determine the key steps in differentiation of the anterior segment that are regulated by Wnt signaling, we expressed Wnt antagonist crescent (CRS) in the embryonic lens. The full–length crescent cDNA was cloned into a double–subgenomic Sindbis virus replicon. The replicon encoding both crescent and GFP marker (rSINm/CRS/GFP) was packaged into viral particles. Chicken lenses were infected with rSINm/CRS/GFP replicon at stages 18 to 24. The embryos were allowed to develop for 1 to 5 days post infection. The resulting phenotype was characterized by immunofluorescence using specific markers for lens, cornea and ciliary epithelium development. Results: The inhibition of Wnt signaling in the anterior part of the eye had a complex effect on eye differentiation. CRS expression inhibited lens epithelium proliferation but promoted primary lens fiber elongation. In severe cases, it led to a significant loss of the anterior lens epithelium. CRS also inhibited corneal epithelium proliferation and formation of the primary cornea. In contrast, differentiation of the corneal endothelium was not affected by CRS expression. Moreover, the corneal endothelium developed, even in the absence of lens epithelium. Conclusions: These results imply that Wnt signaling regulates multiple steps in the development of the anterior structures of the eye. Wnt signaling plays an important role in lens and corneal epithelia proliferation, lens fiber and corneal endothelium differentiation.
Keywords: anterior segment • cornea: endothelium • growth factors/growth factor receptors