Reference Report

Reference
Citation	Takei, Y., Ozawa, Y., Sato, M., Watanabe, A., Tabata, T. (2004). Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans. Development 131(1): 73--82. (Export to RIS)
FlyBase ID	FBrf0167537
Publication Type	Research paper
PubMed ID	14645127
PubMed 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 tout-velu (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.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Development
Title	Development
Publication Year	1987-
ISBN/ISSN	0950-1991
Data from Reference
Aberrations (2)
	Df(2R)Jp8 Df(2R)P34
Alleles (13)
	botv⁴²³ botv⁵¹⁰ botv⁵¹⁴ dpp^{Scer\UAS.E.T:Avic\GFP-EGFP} Ecol\lacZ^dpp-P1552 Ext2³²⁶ Ext2^Scer\UAS.cTa Ext2^αTub84B.PT Scer\GAL4^dpp.blk1 T:Avic\GFP^EGFP ttv²⁰⁵ ttv⁵²⁴ ttv^00681b
Constructs (4)
	P{GAL4-dpp.blk1} P{tub-Ext2.T} P{UAS-dpp.GFP.E} P{UAS-Ext2.T}
Genes (16)
	botv Dll dpp Ecol\lacZ Ext2 hh Mad ptc sala salm salr Scer\GAL4 smo T:Avic\GFP ttv wg
Insertions (1)
	P{PZ}P1552