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Vol. 12, No. 13, pp. 2022-2035, July 1, 1998
Medical Research Council (MRC) Laboratory of Molecular Biology,
Cambridge CB2 2QH, UK
Endoderm induction in Drosophila is mediated by the
extracellular signals Decapentaplegic (Dpp) and Wingless (Wg). We
discovered a secondary signal with a permissive role in this process,
namely Vein, a neuregulin-like ligand that stimulates the epidermal
growth factor receptor (EGFR) and Ras signaling. Dpp and Wg up-regulate vein expression in the midgut mesoderm in two regions
overlapping the Dpp sources. Experiments based on lack of function and
ectopic stimulation of Dpp and EGFR signaling show that these two
pathways are functionally interdependent and that they synergize with
each other, revealing functional intertwining. The transcriptional response elements for the Dpp signal in midgut enhancers from homeotic
target genes are bipartite, comprising CRE sites as well as binding
sites for the Dpp signal-transducing protein Mad. Of these sites, the
CRE seems to function primarily in the response to Ras, the secondary
signal of Dpp. We discuss the potential significance of why an
inductive process might use a secondary signal whose function is
intertwined with that of the primary signal.
[Key Words: Epidermal growth factor receptor; vein; decapentaplegic; Mad binding sites; endoderm induction]
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