Knockdown of PR-DUB subunit calypso in the developing Drosophila eye and wing results in mis-patterned tissues with altered size and shape

The deubiquitinating enzyme BAP1, the catalytic subunit of the PR-DUB complex, is implicated in several cancers, in the familial cancer syndrome BAP1 Tumor Predisposition Syndrome, and in the neurodevelopmental disorder Kury -Isidor syndrome. In Drosophila, there are numerous reports in the literature describing developmental patterning phenotypes for several chromatin regulators including the discovery of Polycomb itself, but corresponding adult morphological phenotypes caused by developmental dysregulation of Drosophila BAP1 ortholog calypso (caly) are less well-described. We report here that knockdown of caly in the eye and wing produce concomitant chromatin dysregulation phenotypes. RNAi to caly in the early eye reduces survival and leads to changes in eye size and shape including eye outgrowths, some of which resemble homeotic transformations whereas others resemble tumor-like outgrowths seen in other fly cancer models. Mosaic eyes containing caly loss-of-function tissue phenocopy caly RNAi. Knocking down caly across the wing disrupts wing shape and patterning including effects on wing vein pattern. This phenotypic characterization reinforces the growing body of literature detailing developmental mis-patterning driven by chromatin dysregulation and serves as a baseline for future mechanistic studies to understand the role of BAP1 in development and disease. ARTICLE SUMMARYPR-DUB catalytic subunit deubiquitinating enzyme BAP1 plays an important role in tumor suppression and chromatin regulation. Whereas many chromatin regulators are well-characterized for their roles in patterning, the mis-patterning phenotypes in adult structure for dysregulating BAP1 ortholog calypso (caly) in development are less well described. We report mis-patterned adult eye and wing phenotypes caused by caly RNAi in the developing eye and wing respectively.