Autumn Dinh

Multiple Hereditary Exostoses (MHE) is an autosomal skeletal disorder that causes the formation of bony outgrowths called osteochondromas. Currently, there are no treatments to inhibit osteochondroma formation or prevent malignancy except surgical removal of the osteochondromas themselves. MHE results from a loss-of-function mutation in EXT1 and EXT2, which are responsible for synthesizing heparan sulfate (HS) chains which are critical to heparan sulfate proteoglycan (HSPG) function. HSPGs serve as co-receptors for multiple growth factors. Previous studies showed that bony outgrowths in MHE patients are induced by ectopic activation of bone morphogenetic protein signaling and/or Indian hedgehog signaling. The explicit molecular mechanism at which this occurs is unknown. Therefore, we intended to establish a drug-screen protocol using HS sulfate inhibitors and substrates on Drosophila melanogaster. Mutant lines homologous to an MHE phenotype were fed HS sulfate inhibitors and substrates and their progeny wings were dissected. Ectopic vein formation was then analyzed between longitudinal vein 2 and longitudinal vein 3. We observed that sodium chlorate enhanced an MHE phenotype, while glucuronic acid suppressed an MHE phenotype. N-acetylglucosamine had no effect. By establishing a drug-screen protocol, future opportunities may open in genetic and pharmacological research to provide physical, mental, and financial relief to MHE patients.