ThreeDrosophilaEXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans

Author:

Takei Yuki1,Ozawa Yutakahiko1,Sato Makoto1,Watanabe Akira1,Tabata Tetsuya1

Affiliation:

1. Institute of Molecular and Cellular Biosciences, University of Tokyo,Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan

Abstract

The signaling molecules Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless(Wg) function as morphogens and organize wing patterning in Drosophila. In the screen for mutations that alter the morphogen activity, we identified novel mutants of two Drosophila genes, sister of tout-velu (sotv) and brother of tout-velu(botv), and new alleles of toutvelu (ttv). The encoded proteins of these genes belong to an EXT family of proteins that have or are closely related to glycosyltransferase activities required for biosynthesis of heparan sulfate proteoglycans (HSPGs). Mutation in any of these genes impaired biosynthesis of HSPGs in vivo, indicating that, despite their structural similarity, they are not redundant in the HSPG biosynthesis. Protein levels and signaling activities of Hh, Dpp and Wg were reduced in the cells mutant for any of these EXT genes to a various degree, Wg signaling being the least sensitive. Moreover, all three morphogens were accumulated in the front of EXT mutant cells, suggesting that these morphogens require HSPGs to move efficiently. In contrast to previous reports that ttv is involved exclusively in Hh signaling, we found that ttv mutations also affected Dpp and Wg. These data led us to conclude that each of three EXT genes studied contribute to Hh, Dpp and Wg morphogen signaling. We propose that HSPGs facilitate the spreading of morphogens and therefore, function to generate morphogen concentration gradients.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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