Genetics, Vol 139, 241-254, Copyright © 1995


INVESTIGATIONS

Genetic Screens to Identify Elements of the decapentaplegic Signaling Pathway in Drosophila

L. A. Raftery, V. Twombly, K. Wharton and W. M. Gelbart
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, and Department of Cell and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138

Pathways for regulation of signaling by transforming growth factor-{beta} family members are poorly understood at present. The best genetically characterized member of this family is encoded by the Drosophila gene decapentaplegic (dpp), which is required for multiple events during fly development. We describe here the results of screens for genes required to maximize dpp signaling during embryonic dorsal-ventral patterning. Screens for genetic interactions in the zygote have identified an allele of tolloid, as well as two novel alleles of screw, a gene recently shown to encode another bone morphogenetic protein-like polypeptide. Both genes are required for patterning the dorsalmost tissues of the embryo. Screens for dpp interactions with maternally expressed genes have identified loss of function mutations in Mothers against dpp and Medea. These mutations are homozygous pupal lethal, engendering gut defects and severely reduced imaginal disks, reminiscent of dpp mutant phenotypes arising during other dpp-dependent developmental events. Genetic interaction phenotypes are consistent with reduction of dpp activity in the early embryo and in the imaginal disks. We propose that the novel screw mutations identified here titrate out some component(s) of the dpp signaling pathway. We propose that Mad and Medea encode rate-limiting components integral to dpp pathways throughout development.


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[Abstract] [Full Text]


Home page
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[Abstract] [Full Text] [PDF]


Home page
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Genes & Dev., October 15, 1997; 11(20): 2679 - 2690.
[Abstract] [Full Text] [PDF]


Home page
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[Abstract] [Full Text] [PDF]


Home page
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[Abstract] [Full Text] [PDF]


Home page
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[Abstract] [PDF]


Home page
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Development, January 11, 1997; 124(22): 4467 - 4480.
[Abstract] [PDF]


Home page
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Development, January 8, 1997; 124(16): 3167 - 3176.
[Abstract] [PDF]


Home page
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Development, January 1, 1997; 124(1): 79 - 89.
[Abstract] [PDF]


Home page
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Development, January 1, 1997; 124(1): 181 - 193.
[Abstract] [PDF]


Home page
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J Hepker, Q. Wang, C. Motzny, R Holmgren, and T. Orenic
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Development, January 1, 1997; 124(2): 549 - 558.
[Abstract] [PDF]


Home page
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Y. Chen, J.-J. Lebrun, and W. Vale
Regulation of transforming growth factor beta - and activin-induced transcription by mammalian Mad proteins
PNAS, November 12, 1996; 93(23): 12992 - 12997.
[Abstract] [Full Text] [PDF]


Home page
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R. J. Lechleider, M. P.d. Caestecker, A. Dehejia, M. H. Polymeropoulos, and A. B. Roberts
Serine Phosphorylation, Chromosomal Localization, and Transforming Growth Factor-beta Signal Transduction by Human bsp-1
J. Biol. Chem., July 26, 1996; 271(30): 17617 - 17620.
[Abstract] [Full Text] [PDF]


Home page
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Development, July 1, 1996; 122(7): 2153 - 2162.
[Abstract] [PDF]


Home page
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G Q Zhao, K Deng, P A Labosky, L Liaw, and B L Hogan
The gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse.
Genes & Dev., July 1, 1996; 10(13): 1657 - 1669.
[Abstract] [PDF]


Home page
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Mothers against dpp encodes a conserved cytoplasmic protein required in DPP/TGF-beta responsive cells
Development, January 7, 1996; 122(7): 2099 - 2108.
[Abstract] [PDF]


Home page
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Development, January 10, 1995; 121(10): 3393 - 3403.
[Abstract] [PDF]


Home page
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Repression of Dpp Targets by Binding of Brinker to Mad Sites
J. Biol. Chem., May 18, 2001; 276(21): 18216 - 18222.
[Abstract] [Full Text] [PDF]