Drosophila glypican Dally regulates Upd distribution and JAK/STAT signaling activity in eye development. Jia You¹, Yan Zhang², Wenyan Ren², Xinhua Lin^1,2. 1) Dev Biol, Cincinnati Chld Hosp Med Ctr, Cincinnati, Oh; 2) 1State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

   Highly conserved janus kinase (JAK)-signal transducer and activator of transcription(STAT) pathway is a well-known signaling system that is involved in numerous biological processes. In Drosophila, this low-redundant signaling cascade is activated by ligands of Unpaired(Upd) family. Therefore the regulation of Upd distribution is one of the key issues in controlling JAK/STAT signal. Heparan sulfate proteoglycans (HSPGs) are macromolecules that regulate distribution of many ligand proteins including Wingless, Hedgehog and Decapentaplegic(Dpp). Here we show that during Drosophila eye development, HSPGs are also required in normal Upd distribution and JAK/STAT signaling activity. Loss of HSPG biosynthesis enzyme Brother of tout-velu(Botv), Sulfateless (Sfl), or glypican Division abnormally delayed(Dally) and Dally-like protein(Dlp) will lead to reduced levels of Upd and reduction of JAK/STAT signaling activity. Overexpression of Dally is sufficient to accumulate Upd and up-regulate the signaling activity. In vitro luciferase assay also shows that Dally promotes JAK/STAT signaling activity, and is dependent on its heparin sulfate chains. These data suggest that Dally is a major regulator of Upd distribution and JAK/STAT signaling activity.