The Effects of the Oxylosyltransferase Mutation on Wg, Hh, and DPP/TGF-β Signaling
Date
2012-05
Authors
Liu, Alicia
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
The o-xylosyltransferase (oxt) encodes a glycosyltransferase needed for the first step of proteoglycan glycosaminoglycan (GAG) biosynthesis. Disruptions in heparan sulfate proteoglycan (HSPG) biosynthesis change the extracellular environment, which has been shown to block Wingless (Wg)/Wnt, Hedgehog (Hh), and Decapentaplegic (Dpp)/TGF-β intercellular signaling. Therefore, mutations in oxt are predicted to disrupt normal Wg, Hh, and Dpp signaling due to the absence of heparan sulfate (HS) and chondroitan sulfate (CS) modified extracellular proteoglycans. Characterization of the oxt mutant in Drosophila wing discs shows this mutation caused unexpectedly mild signaling defects as compared with other mutants acting further down in the HS biosynthetic pathway, such as sulfateless (sfl), which is responsible for specific downstream sulfation and activation of only HS chains. The oxt-sfl double mutant was made to address why the oxt phenotype is less severe. Clonal analysis shows that the double mutant looks more like sfl, suggesting the oxt null mutation does not yield a fully penetrant phenotype, allowing some xylose addition to the core proteoglycan upon which Sfl can act. Because the oxt mutation is a nonsense mutation that eliminates the Oxt active site, the lack of penetrance can be attributed to either perdurance of residual Oxt protein or mRNA in mutant cells.
Description
Keywords
o-xylosyltransferase (oxt) , Wg, Hh, and DPP/TGF-β signaling