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Vol. 12, No. 15, pp. 2354-2370, August 1, 1998
1 Brookdale Center for Developmental and Molecular
Biology, Mount Sinai School of Medicine, New York, New York 10029 USA;
2 Department of Molecular Genetics and Cell Biology,
University of Chicago, Chicago, Illinois 60637 USA
Dorsal mesoderm induction in arthropods and ventral mesoderm
induction in vertebrates are closely related processes that involve signals of the BMP family. In Drosophila, induction of visceral mesoderm, dorsal muscles, and the heart by Dpp is, at least in part,
effected through the transcriptional activation and function of the
homeobox gene tinman in dorsal mesodermal cells during early
embryogenesis. Here we present a functional dissection of a
tinman enhancer that mediates the Dpp response. We provide
evidence that mesoderm-specific induction of tinman requires
the binding of both activators and repressors. Screens for binding
factors yielded Tinman itself and the Smad4 homolog Medea. We show that the binding and synergistic activities of Smad and Tinman proteins are
critical for mesodermal tinman induction, whereas repressor binding sites prevent induction in the dorsal ectoderm and amnioserosa. Thus, integration of positive and negative regulators on enhancers of
target genes appears to be an important mechanism in tissue-specific induction by TGF-
molecules.
[Key Words: mesoderm induction; tinman; dpp; Medea; Mad; Smad; signal transduction; enhancer]
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