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Distalization of the Drosophila leg by graded EGF-receptor activity

Nature volume 418, pages 781–785 (2002)Cite this article

Abstract

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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References

  1. Campbell, G., Weaver, T. & Tomlinson, A. Axis specification in the developing Drosophila appendage: the role of wingless, decapentaplegic, and the homeobox gene aristaless. Cell 74, 1113–1123 (1993)

    Article  CAS  Google Scholar 

  2. Diaz-Benjumea, F. J., Cohen, B. & Cohen, S. M. Cell interaction between compartments establishes the proximal-distal axis of Drosophila legs. Nature 372, 175–179 (1994)

    Article  CAS  Google Scholar 

  3. Lecuit, T. & Cohen, S. M. Proximal-distal axis formation in the Drosophila leg. Nature 288, 139–145 (1997)

    Article  Google Scholar 

  4. Martin, G. R. The roles of FGFs in the early development of vertebrate limbs. Genes Dev. 12, 1571–1586 (1998)

    Article  CAS  Google Scholar 

  5. Panganiban, G. et al. The origin and evolution of animal appendages. Proc. Natl Acad. Sci. USA 94, 5162–5166 (1997)

    Article  CAS  Google Scholar 

  6. Shubin, N., Tabin, C. & Carroll, S. Fossils, genes and the evolution of animal limbs. Nature 388, 639–648 (1997)

    Article  CAS  Google Scholar 

  7. Campbell, G. & Tomlinson, A. Initiation of the proximodistal axis in insect legs. Development 121, 619–628 (1995)

    CAS  Google Scholar 

  8. Casares, F. & Mann, R. S. The ground state of the ventral appendage in Drosophila. Science 293, 1477–1480 (2001)

    Article  CAS  Google Scholar 

  9. Wehrli, M. et al. arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 407, 527–530 (2000)

    Article  CAS  Google Scholar 

  10. Nellen, D., Affolter, M. & Basler, K. Receptor serine/threonine kinases implicated in the control of Drosophila body pattern by decapentaplegic. Cell 78, 225–237 (1994)

    Article  CAS  Google Scholar 

  11. Penton, A. et al. Identification of two bone morphogenetic protein type I receptors in Drosophila and evidence that Brk25D is a decapentaplegic receptor. Cell 78, 239–250 (1994)

    Article  CAS  Google Scholar 

  12. Clifford, R. J. & Schupbach, T. Coordinately and differentially mutable activities of torpedo, the Drosophila melanogaster homolog of the vertebrate EGF receptor gene. Genetics 123, 771–787 (1989)

    CAS  Google Scholar 

  13. Campbell, G. & Tomlinson, A. The roles of the homeobox genes aristaless and Distal-less in patterning the legs and wings of Drosophila. Development 125, 4483–4493 (1998)

    CAS  Google Scholar 

  14. Kumar, J. P. et al. Dissecting the roles of the Drosophila EGF receptor in eye development and MAP kinase activation. Development 125, 3875–3885 (1998)

    CAS  Google Scholar 

  15. Halfar, K., Rommel, C., Stocker, H. & Hafen, E. Ras controls growth, survival and differentiation in the Drosophila eye by different thresholds of MAP kinase activity. Development 128, 1687–1696 (2001)

    CAS  Google Scholar 

  16. Kojima, T., Sato, M. & Saigo, K. Formation and specification of distal leg segments in Drosophila by dual Bar homeobox genes, BarH1 and BarH2. Development 127, 769–778 (2000)

    CAS  Google Scholar 

  17. Couso, J. P. & Bishop, S. A. Proximo-distal development in the legs of Drosophila. Int. J. Dev. Biol. 42, 345–352 (1998)

    CAS  Google Scholar 

  18. Schweitzer, R. & Shilo, B. Z. A thousand and one roles for the Drosophila EGF receptor. Trends Genet. 13, 191–196 (1997)

    Article  CAS  Google Scholar 

  19. Bang, A. G. & Kintner, C. Rhomboid and Star facilitate presentation and processing of the Drosophila TGF-α homolog Spitz. Genes Dev. 14, 177–186 (2000)

    CAS  Google Scholar 

  20. Wasserman, J. D., Urban, S. & Freeman, M. A family of rhomboid-like genes: Drosophila rhomboid-1 and roughoid/rhomboid-3 cooperate to activate EGF receptor signaling. Genes Dev. 14, 1651–1663 (2000)

    CAS  Google Scholar 

  21. Kramer, S., Okabe, M., Hacohen, N., Krasnow, M. A. & Hiromi, Y. Sprouty: a common antagonist of FGF and EGF signaling pathways in Drosophila. Development 126, 2515–2525 (1999)

    CAS  Google Scholar 

  22. Casci, T., Vinos, J. & Freeman, M. Sprouty, an intracellular inhibitor of Ras signaling. Cell 96, 655–665 (1999)

    Article  CAS  Google Scholar 

  23. Irvine, K. D. Fringe Notch, and making developmental boundaries. Curr. Opin. Genet. Dev. 9, 434–441 (1999)

    Article  CAS  Google Scholar 

  24. Queenan, A. M., Ghabrial, A. & Schupbach, T. Ectopic activation of torpedo/Egfr, a Drosophila receptor tyrosine kinase, dorsalizes both the eggshell and the embryo. Development 124, 3871–3880 (1997)

    CAS  Google Scholar 

  25. Brook, W. J. & Cohen, S. M. Antagonistic interactions between wingless and decapentaplegic responsible for dorsal-ventral pattern in the Drosophila leg. Science 273, 1373–1377 (1996)

    Article  CAS  Google Scholar 

  26. Mardon, G., Solomon, N. M. & Rubin, G. M. dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila. Development 120, 3473–3486 (1994)

    CAS  Google Scholar 

  27. Struhl, G. & Basler, K. Organizing activity of wingless protein in Drosophila. Cell 72, 527–540 (1993)

    Article  CAS  Google Scholar 

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Acknowledgements

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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  1. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA

    Gerard Campbell

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  1. Gerard Campbell
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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). https://doi.org/10.1038/nature00971

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