Phenotypic Characterization of the 7H24 Mutant in O‐xylosyltransferase

Abstract

Formation of morphogenetic gradients is a fundamental mechanism of developmental signaling. Establishment of the gradient dictates how tissues respond to extracellular signals to elicit appropriate cellular responses to a secreted ligand. Recently, we have identified a novel mutation in the Drosophila O‐xylosyltransferase (oxt) that encodes a key enzyme required for heparan and chondroitin sulfate (HS and CS) biosynthesis, named 7H24. In Drosophila, HS has been shown to be essential for Wingless (Wg)/Wnt, Hedgehog (Hh) and Decapentaplegic (Dpp)/Bone Morphogenic Protein (BMP) extracellular ligand movement and gradient formation. When HS is absent downstream signaling of these elemental pathways that drive the Drosophila and human developmental program is disrupted. The 7H24 mutation in oxt is a functional null and removal of maternal and zygotic oxt is embryonic lethal with terminal segment polarity cuticle phenotypes suggesting disruption of the Wg and/or Hh signaling pathway. Removal of zygotic oxt causes homozygous mutants to die as pharate adults with small rough eyes and thorax defects that cannot close from the pupal case. We find deficiencies in Wg, Hh and Dpp signaling in the mutant larval wing imaginal discs and evaluation of larval eye phenotypes suggests they do not arise because of defects in cell type specification.