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

ABSTRACT: Drosophila Lobe (L) alleles were first discovered ∼100 years ago as spontaneous dominant mutants with characteristic developmental eye defects. However, the molecular basis for L dominant eye phenotypes has not been clearly understood. A previous work reported identification of CG10109/PRAS40 as the L gene, but subsequent analyses suggested that PRAS40 may not be related to L Here, we revisited the L gene to clarify this discrepancy and understand the basis for the dominance of L mutations. Genetic analysis localized the L gene to Oaz, which encodes a homolog of the vertebrate zinc finger protein 423 (Zfp423) family transcriptional regulators. We demonstrate that RNAi knockdown of Oaz almost completely restores all L dominant alleles tested. L^rev6-3 , a revertant allele of the L² dominant eye phenotype, has an inframe deletion in the Oaz coding sequence. Molecular analysis of L dominant mutants identified allele-specific insertions of natural transposons (roo[ ]L¹ , hopper[ ]L⁵ , and roo[ ]L^r ) or alterations of a preexisting transposon (L² -specific mutations in roo[ ]Mohr) in the Oaz region. In addition, we generated additional L² -reversion alleles by CRISPR targeting at Oaz These new loss-of-function Oaz mutations suppress the dominant L eye phenotype. Oaz protein is not expressed in wild-type eye disc but is expressed ectopically in L²/+ mutant eye disc. We induced male recombination between Oaz-GAL4 insertions and the L² mutation through homologous recombination. By using the L² -recombined GAL4 reporters, we show that Oaz-GAL4 is expressed ectopically in L² eye imaginal disc. Taken together, our data suggest that neomorphic L eye phenotypes are likely due to misregulation of Oaz by spontaneous transposon insertions.

SUBMITTER: Son W 

PROVIDER: S-EPMC7463288 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature