The Classic Eye Phenotype of Is Caused by Transposon Insertion-Induced Misexpression of a Zinc-Finger Transcription Factor.

() alleles were first discovered ∼100 years ago as spontaneous dominant mutants with characteristic developmental eye defects. However, the molecular basis for dominant eye phenotypes has not been clearly understood. A previous work reported identification of as the gene, but subsequent analyses suggested that may not be related to Here, we revisited the gene to clarify this discrepancy and understand the basis for the dominance of mutations. Genetic analysis localized the gene to , which encodes a homolog of the vertebrate zinc finger protein 423 (Zfp423) family transcriptional regulators. We demonstrate that RNAi knockdown of almost completely restores all dominant alleles tested. , a revertant allele of the dominant eye phenotype, has an inframe deletion in the coding sequence. Molecular analysis of dominant mutants identified allele-specific insertions of natural transposons ( , , and ) or alterations of a preexisting transposon ( -specific mutations in ) in the region. In addition, we generated additional -reversion alleles by CRISPR targeting at These new loss-of-function mutations suppress the dominant eye phenotype. Oaz protein is not expressed in wild-type eye disc but is expressed ectopically in mutant eye disc. We induced male recombination between insertions and the mutation through homologous recombination. By using the -recombined GAL4 reporters, we show that is expressed ectopically in eye imaginal disc. Taken together, our data suggest that neomorphic eye phenotypes are likely due to misregulation of by spontaneous transposon insertions.