Hedgehog activates the EGF receptor pathway during Drosophila head development.
The Hedgehog (Hh) and Epidermal growth factor receptor (EGFR) signaling pathways play critical roles in pattern formation and cell proliferation in invertebrates and vertebrates. In this study, we demonstrate a direct link between these two pathways in Drosophila melanogaster. Hh and EGFR signaling are each required for the formation of a specific region of the head of the adult fruitfly. We show that hh and vein (vn), which encodes a ligand of the Drosophila EGFR (Schnepp, B., Grumbling, G., Donaldson, T. and Simcox, A. (1996) Genes Dev. 10, 2302-13), are expressed in adjacent domains within the imaginal primordium of this region. Using loss- and gain-of-function approaches, we demonstrate that Hh activates vn expression. We also show that Hh activation of vn is mediated through the gene cubitus interruptus (ci) and that this activation requires the C-terminal region of the Ci protein. Finally, we demonstrate that wingless (wg) represses vn expression, thereby limiting the domain of EGFR signaling.
Amin
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Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6074, USA.
Li
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Y
Finkelstein
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R
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000254:growth & development*; D029721:Drosophila Proteins; D066246:ErbB Receptors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006257:Head / Q000254:growth & development* / Q000502:physiology; D053823:Hedgehog Proteins; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020880:Neuregulins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051155:Wnt1 Protein
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D020880:Neuregulins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C092937:ci protein, Drosophila; C074622:wg protein, Drosophila; C077245:hh protein, Drosophila; C102104:vn protein, Drosophila; D066246:ErbB Receptors