Wnt-Frizzled signaling is critical for neuronal development and disease.We have explored thecontribution of Frizzled receptor Fz8 to eye/retinal phenotypes in combination with Fz5. During retinaldevelopment,Fz8 expression overlaps with Fz5 and is observed in the neural retina and optic fissure/disc.TheFz8-/- mice exhibit mild optic disc defect and increased astrocyte counts.Embryos lacking both Fz5 and Fz8die in early development.However,a majority of triallelic Fz5-/-;Fz8+/- mutants that survive until birthdevelop severe retinal coloboma and microphthalmia with full penetrance,which is not detected in Fz5-/- mice.We show that impaired retinal neurogenesis is caused by increased cell cycle exit of progenitors inFz5-/-;Fz8+/- mutants,resulting in higher proportion of early-born retinal neurons such as ganglion,amacrineand cone cells.Furthermore,double mutant retinas have disorganized retinal neuroblasts,perturbed apical-basalpolarity and compromised Notch signaling,implying a role for Frizzled receptors in maintaining theorganization of retinal neuroepithelium.In concordance,in vitro inhibition of Fz8 and Fz5 receptors leads torandomized division of progenitors along the retinal neuroblast layer.In an occasional compound mutant thatsurvives to young adult stage,both retinal ganglion and horizontal cell axons show defasciculation andsprouting into the inner plexiform layer.Our studies implicate a dose-dependent regulation of optic fissure/discformation,progenitor expansion and axonal integrity by Fz8 and Fz5 signaling during retinal development.