The cell-surface proteoglycan Dally regulates Wingless signalling in Drosophila.
Wingless (Wg) is a member of the Wnt family of growth factors, secreted proteins that control proliferation and differentiation during development. Studies in Drosophila have shown that responses to Wg require cell-surface heparan sulphate, a glycosaminoglycan component of proteoglycans. These findings suggest that a cell-surface proteoglycan is a component of a Wg/Wnt receptor complex. We demonstrate here that the protein encoded by the division abnormally delayed (dally) gene is a cell-surface, heparan-sulphate-modified proteoglycan. dally partial loss-of-function mutations compromise Wg-directed events, and disruption of dally function with RNA interference produces phenotypes comparable to those found with RNA interference of wg or frizzled (fz)/Dfz2. Ectopic expression of Dally potentiates Wg signalling without altering levels of Wg and can rescue a wg partial loss-of-function mutant. We also show that dally, a regulator of Decapentaplegic (Dpp) signalling during post-embryonic development, has tissue-specific effects on Wg and Dpp signalling. Dally can therefore differentially influence signalling mediated by two growth factors, and may form a regulatory component of both Wg and Dpp receptor complexes.
Tsuda
M
M
Department of Biology, Tokyo Metropolitan University, Japan.
Kamimura
K
K
Nakato
H
H
Archer
M
M
Staatz
W
W
Fox
B
B
Humphrey
M
M
Olson
S
S
Futch
T
T
Kaluza
V
V
Siegfried
E
E
Stam
L
L
Selleck
S B
SB
D000818:Animals; D030801:Animals, Genetically Modified; D003001:Cloning, Molecular; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins; D004817:Epidermis / Q000196:embryology / Q000502:physiology; D005260:Female; D017344:Genes, Insect; D005821:Genetic Techniques; D005835:Genitalia / Q000196:embryology; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000502:physiology; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D019476:Insect Proteins / Q000502:physiology; D007814:Larva / Q000737:chemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012313:RNA / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D051155:Wnt1 Protein
D029721:Drosophila Proteins; C063459:En protein, Drosophila; D017261:Glycosylphosphatidylinositols; D019812:Heparan Sulfate Proteoglycans; D018398:Homeodomain Proteins; D019476:Insect Proteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C098128:dally protein, Drosophila; C064196:dpp protein, Drosophila; C074622:wg protein, Drosophila; D012313:RNA