Modelling Robinow Syndrome in the Fruit Fly

Abstract

Model organisms are non-human species used to study fundamental biological processes, with common examples including mice, frogs, roundworms, and the fruit fly Drosophila melanogaster. The fruit fly has been a cornerstone of biological research for over a century due to its low cost, short life cycle, and powerful genetic tools. Notably, approximately 75% of human disease-associated genes have counterparts in the fruit fly, making it a valuable system for modeling human disease. This has allowed the Verheyen lab to study a rare developmental disorder known as Robinow Syndrome (RS), a disorder that in humans is associated with a range of skeletal abnormalities, including abnormalities to the face and head, as well as a shortening of the limbs. By using a genetic system known as the GAL4-UAS system, which enables targeted manipulation of gene expression in specific tissues, we were able to express the human disease associated genes in the fruit fly. In particular, we expressed two Frizzled2 human patient variants, allowing us to mimic and study the role that they play in the development of the disorder. We found that the Frizzled2 patient variants were sufficient to cause the disorder in the fruit fly, providing insight into their roles in the development of the disorder in humans. These studies help us to better understand how this disorder occurs in humans and may help guide future therapeutic strategies.