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Distalization of the Drosophila leg by graded EGF-receptor activity


Arthropods and higher vertebrates both possess appendages, but these are morphologically distinct and the molecular mechanisms regulating patterning along their proximodistal axis (base to tip) are thought to be quite different. In Drosophila, gene expression along this axis is thought to be controlled primarily by a combination of transforming growth factor-β (TGF-ß) and Wnt signalling from sources of ligands, Decapentaplegic (Dpp) and Wingless (Wg), in dorsal and ventral stripes, respectively1,2,3. In vertebrates, however, proximodistal patterning is regulated by receptor tyrosine kinase (RTK) activity from a source of ligands, fibroblast growth factors (FGFs), at the tip of the limb bud4. Here I revise our understanding of limb development in flies and show that the distal region is actually patterned by a distal-to-proximal gradient of RTK activity, established by a source of epidermal growth factor (EGF)-related ligands at the presumptive tip. This similarity between proximodistal patterning in vertebrates and flies supports previous suggestions5,6 of an evolutionary relationship between appendages/body-wall outgrowths in animals.

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Figure 1: Proximodistal axis of the wild-type (WT) leg and regulation of al expression by Wg and Dpp signalling.
Figure 2: Regulation of tarsal development by EGFR signalling.
Figure 3: Expression and activity of EGFR ligands in the tarsus.
Figure 4: Temporal requirement for EGFR signalling.


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I thank A. Tomlinson, M. Simcox, D. Chapman and R. Carthew for advice and comments on the manuscript. I also thank the following for stocks and reagents: K. Moses, J. Kumar, M. Werhli, A. Simcox, J. P. Couso, S. Kunes, T. Schubach, T. Volk, G. Struhl, H. M. Chung, M. Feeman, R. Cagan, T. Kojima, S. Cohen, K. Cook, K. Matthews, the Bloomington Stock Center, J. P. Vincent, and the Developmental Studies Hybridoma Bank.

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Correspondence to Gerard Campbell.

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Campbell, G. Distalization of the Drosophila leg by graded EGF-receptor activity. Nature 418, 781–785 (2002).

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