Arrested differentiation and epithelial cell degeneration in zebrafish lens mutants

In a chemical mutagenesis screen, we identified two zebrafish mutants that possessed small pupils. Genetic complementation revealed these two lines ar e due to mutations in different genes. The phenotypes of the two mutants we re characterized using histologic, immunohistochemical, and tissue transpla ntation techniques. The arrested lens (arl) mutant exhibits a small eye and pupil phenotype at 48 hr postfertilization (hpf) and lacks any histologica lly identifiable lens structures by 5 days postfertilization (dpf). In cont rast, the disrupted lens (dsl) mutants are phenotypically normal until 5 dp f, and then undergo lens disorganization and cell degeneration that is appa rent by 7 dpf. Histology reveals the arl mutant terminates lens cell differ entiation by 48 hpf, whereas the dsl lens exhibits a defective lens epithel ial cell population at 5 dpf. Lens transplantation experiments demonstrate both mutations are autonomous to the lens tissue. Immunohistochemistry reve als the retinal cells may suffer subtle effects, possibly due to the lens a bnormalities. (C) 2001 Wiley-Liss, Inc.