The disarrayed mutation results in cell cycle and neurogenesis defects during retinal development in zebrafish

Background: The vertebrate retina is derived from proliferative neuroepithelial cells of the optic cup. During retinal development, cell proliferation and the processes of cell cycle exit and neurogenesis are coordinated in neuroepithelial progenitor cells. Previous studies have demonstrated reciprocal influences between the cell cycle and neurogenesis. However the specific mechanisms and exact relationships of cell cycle regulation and neurogenesis in the vertebrate retina remain largely unknown. Results: We have isolated and characterized a zebrafish mutant, disarrayed (dry(a64)), which exhibits retinal defects in cell cycle regulation and neurogenesis. By 42 hours post fertilization, disarrayed mutants show small eyes and a reduced forebrain. Other aspects of development appear normal. Although retinogenesis is delayed, mutant retinal cells eventually differentiate to all major cell types. Examination of the disarrayed mitotic cycle using BrdU and direct imaging techniques revealed that retinal neuroepithelial cells have an extended cell cycle period and reduced rate of cell cycle exit and neurogenesis, despite the fact that neurogenesis initiates at the appropriate time of development. Genetic mosaic analyses indicate that the cell cycle phenotype of disarrayed is cell-non-autonomous. Conclusion: The disarrayed mutant shows defects in both cell cycle regulation and neurogenesis and provides insights into the coordinated regulation of these processes during retinal development.