Mothers against dpp encodes a conserved cytoplasmic protein required in DPP/TGF-beta responsive cells.
The proteins necessary for signal transduction in cells responding to ligands of the TGF-beta family are largely unknown. We have previously identified Mad (Mothers against dpp), a gene that interacts with the TGF-beta family member encoded by decapentaplegic (dpp) in Drosophila. Assay of Mad's role in the DPP-dependent events of embryonic midgut development demonstrates that Mad is required for any response of the visceral mesoderm or endoderm to DPP signals from the visceral mesoderm. Replacement of the normal DPP promoter with a heterologous (hsp70) promoter fails to restore DPP-dependent responses in Mad mutant midguts. Experiments utilizing Mad transgenes regulated by tissue-specific promoters show that MAD is required specifically in cells responding to DPP. Immunohistochemical studies localize MAD to the cytoplasm in all tissues examined. Experiments in Xenopus embryos demonstrate that Drosophila MAD can function in the signaling pathway of BMP-4, a vertebrate homolog of dpp. Based on these results, we propose that Mad is a highly conserved and essential element of the DPP signal transduction pathway.
Newfeld
S J
SJ
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Chartoff
E H
EH
Graff
J M
JM
Melton
D A
DA
Gelbart
W M
WM
D000818:Animals; D015153:Blotting, Western; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000235:genetics; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology; D004742:Enhancer Elements, Genetic / Q000502:physiology; D017930:Genes, Reporter; D007301:Insect Hormones / Q000235:genetics* / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014981:Xenopus / Q000196:embryology / Q000235:genetics
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D007301:Insect Hormones; C112506:MAD protein, Drosophila; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C064196:dpp protein, Drosophila; D012194:RNA-Directed DNA Polymerase