Developmental delay during eye morphogenesis underlies optic cup and neurogenesis defects in zebrafish mutants.

Shaping the vertebrate eye requires evagination of the optic vesicles. These vesicles subsequently fold into optic cups prior to undergoing neurogenesis and allocating a population of late progenitors at the margin of the eye. encodes a protein of unknown biological function expressed in the developing optic vesicles, and loss of function results in malformed eyes. The bases of these defects are, however, poorly understood. To further study we used CRISPR/Cas9 to generate a new zebrafish mutant allele (). We characterized eye morphogenesis and neurogenesis upon loss of function using tissue/cell-type-specific transgenes and immunostaining, hybridization and bromodeoxyuridine incorporation. eyes fail to grow properly and display an excess of progenitors in the ciliary marginal zone. The expression of a transgene reporter for the gene -a conserved marker for retinal progenitors- was delayed in mutant eyes and accompanied by disruptions in the epithelial folding that fuels optic cup morphogenesis. Mutants also displayed nasal-temporal malformations suggesting asynchronous development along that axis. Consistently, nasal retinal neurogenesis initiated but did not propagate in a timely fashion to the temporal retina. Later in development, mutant retinas did laminate and differentiate. Thus, mutants present a complex eye morphogenesis phenotype characterized by an organ-specific developmental delay. We propose that facilitates optic cup development with consequences both for timely neurogenesis and allocation of progenitors to the zebrafish ciliary marginal zone. These results confirm and extend previous analyses supporting the role of in coordinating morphogenesis and differentiation in developing eyes.