Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling.
We have identified the Drosophila UDP-glucose dehydrogenase gene as being involved in wingless signaling. Mutations in this gene, called kiwi, generate a phenotype identical to that of wingless. UDP-glucose dehydrogenase is required for the biosynthesis of UDP-glucuronate, which in turn is utilized in the biosynthesis of glycosaminoglycans. By rescuing the kiwi phenotype with both UDP-glucuronate and the glycosaminoglycan heparan sulfate, we show that kiwi function in the embryo is crucial for the production of heparan sulfate in the extracellular matrix. Further, injection of heparin degrading enzyme, heparinase (and not chondroitin, dermatan or hyaluronic acid degrading enzyme) into wild-type embryos leads to the degradation of heparin-like glycosaminoglycans and a 'wingless-like' cuticular phenotype. Our study thus provides the first genetic evidence for the involvement of heparin-like glycosaminoglycans in signal transduction.
Binari
R C
RC
Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto, Canada.
Staveley
B E
BE
Johnson
W A
WA
Godavarti
R
R
Sasisekharan
R
R
Manoukian
A S
AS
D000595:Amino Acid Sequence; D000818:Animals; D002999:Clone Cells; D018076:DNA, Complementary / Q000235:genetics; D004330:Drosophila / Q000196:embryology; D029721:Drosophila Proteins; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D017344:Genes, Insect; D015698:Genomic Library; D006493:Heparin / Q000378:metabolism*; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014533:Uridine Diphosphate Glucose Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D018076:DNA, Complementary; D029721:Drosophila Proteins; D019476:Insect Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; C074622:wg protein, Drosophila; D006493:Heparin; D014533:Uridine Diphosphate Glucose Dehydrogenase