Mutation of frizzled8a delays neural retinal cell differentiation and results in microphthalmia in zebrafish

Abstract

Eye formation in vertebrates involves highly coordinated processes, and the differentiation of various eye tissues is regulated by conserved transcription factors and signalling pathways. Mutations in key genes of the regulatory hierarchy lead to congenital disorders and ocular diseases. The Wnt signalling pathway plays a key role in different aspects of eye development, and several Wnt receptors of the Frizzled family are required for eye specification and differentiation. However, their precise function in these processes remains elusive. Here we show that mutation of the frizzled8a gene in zebrafish leads to microphthalmia. The differentiation of retinal layers is delayed, and retinal progenitor cells in microphthalmic embryos fail to normally exit the cell cycle to enter into the post-mitotic state. They exhibit delayed differentiation associated with enhanced apoptosis, which results in abnormal lamination of retinal layers, reduction in the number of retinal cells, and small eye phenotype. These findings suggest that Frizzled8a plays a specific role in regulating cell cycle progression during the differentiation of retinal progenitor cells.