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Proximal–distal axis formation in the Drosophila leg

Abstract

Limb development requires the formation of a proximal–distal axis perpendicular to the main anterior–posterior and dorsal–ventral body axes. The secreted signalling proteins Decapentaplegic and Wingless act in a concentration-dependent manner to organize the proximal–distal axis. Discrete domains of proximal–distal gene expression are defined by different thresholds of Decapentaplegic and Wingless activities. Subsequent modulation of the relative sizes of these domains by growth of the leg is required to form the mature pattern.

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Figure 1: Subdivision of the P–D axis by expression of Dll and Dac.
Figure 2: Wg and Dpp do not act by relay of another signal to induce Dll.
Figure 3: Wg signalling is required for induction, but not maintenance, of Dll and Dac.
Figure 4: Dpp signalling is required for induction, but not maintenance, of Dll and Dac.
Figure 5: Distinct thresholds for activation of Dll and Dac by Wg and Dpp.
Figure 6: Repression of Dac by high levels of Wg and Dpp.
Figure 7: Roles of Wg and Dpp in the D–V and P–D axes.

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References

  1. Brook, W. J., Diaz-Benjumea, F. J. & Cohen, S. M. Organizing spatial pattern in limb development. Annu. Rev. Cell Dev. Biol. 12, 161–180 (1996).

    Article  CAS  Google Scholar 

  2. Lawrence, P. A. & Struhl, G. Morphogens, compartments and pattern: lessons from Drosophila? Cell 85, 951–961 (1996).

    Article  CAS  Google Scholar 

  3. Diaz-Benjumea, F. J. & Cohen, S. M. Interaction between dorsal and ventral cells in the imaginal disc directs wing development in Drosophila. Cell 75, 741–752 (1993).

    Article  CAS  Google Scholar 

  4. Basler, K. & Struhl, G. Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein. Nature 368, 208–214 (1994).

    Article  ADS  CAS  Google Scholar 

  5. Tabata, T. & Kornberg, T. Hedgehog is a signalling protein with a key role in patterning Drosophila imaginal discs. Cell 76, 89–102 (1994).

    Article  CAS  Google Scholar 

  6. Williams, J. A., Paddock, S. w., Vorwerk, K. & Carroll, S. B. Organization of wing formation and induction of a wing-patterning gene at the dorsal/ventral compartment boundary. Nature 368, 299–305 (1994).

    Article  ADS  CAS  Google Scholar 

  7. Irvine, K. & Wieschaus, E. fringe, a boundary specific signalling molecule, mediates interactions between dorsal and ventral cells during Drosophila wing development. Cell 79, 595–606 (1994).

    Article  CAS  Google Scholar 

  8. Kim, J., Irvine, K. D. & Carroll, S. B. Cell recognition, signal induction and symmetrical gene activation at the dorsal/ventral boundary of the developing Drosophila wing. Cell 82, 795–802 (1995).

    Article  CAS  Google Scholar 

  9. Diaz-Benjumea, F. J. & Cohen, S. M. Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. Development 121, 4215–4225 (1995).

    CAS  PubMed  Google Scholar 

  10. Zecca, M., Basler, K. & Struhl, G. Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing. Development 121, 2265–2278 (1995).

    CAS  PubMed  Google Scholar 

  11. Nellen, D., Burke, R., Struhl, G. & Basler, K. Direct and long-range action of a Dpp morphogen gradient. Cell 85, 357–368 (1996).

    Article  CAS  Google Scholar 

  12. Lecuit, T. et al. Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing. Nature 381, 387–393 (1996).

    Article  ADS  CAS  Google Scholar 

  13. Singer, M. A., Penton, A., Twombly, V., Hoffmann, F. M. & Gelbart, W. M. Signaling through both type I Dpp receptors is required for anterior-posterior patterning of the entire Drosophila wing. Development 124, 79–89 (1997).

    CAS  PubMed  Google Scholar 

  14. Neumann, C. J. & Cohen, S. M. Ahierarchy of cross-regulation involving Notch, wingless, vestigal and cut organizes the dorsal/ventral axis of the Drosophila wing. Development 122, 3477–3485 (1996).

    CAS  PubMed  Google Scholar 

  15. Zecca, M., Basler, K. & Struhl, G. Direct and long-range action of a Wingless morphogen gradient. Cell 87, 833–844 (1996).

    Article  CAS  Google Scholar 

  16. Neumann, C. J. & Cohen, S. M. Long-range action of Wingless organizes the dorsal–ventral axis of the Drosophila wing. Development 124, 871–880 (1997).

    CAS  Google Scholar 

  17. Brook, W. J. & Cohen, S. M. Antagonistic interactions between Wingless and Decapentaplegic responsible for dorsal–ventral pattern in the Drosophila leg. Science 273, 1371–1377 (1996).

    Article  ADS  Google Scholar 

  18. Jiang, J. & Struhl, G. Complementary and mutually exclusive activities of Decapentaplegic and Wingless organize axial pattern during Drosophila limb development. Cell 86, 401–409 (1996).

    Article  CAS  Google Scholar 

  19. Penton, A. & Hoffmann, F. M. Decapentaplegic restricts the domain of wingless during Drosophila limb patterning. Nature 382, 162–165 (1996).

    Article  ADS  CAS  Google Scholar 

  20. Couso, J. P., Bate, M. & Martinez Arias, A. A wingless -dependent polar coordinate system in the imaginal discs of Drosophila. Science 259, 484–489 (1993).

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  23. Held, L. I. J., Heup, M. A., Sappington, J. M. & Peters, S. D. Interactions of decapentaplegic, wingless and Distal-less in the Drosophila leg. Wilhelm Roux Arch. Dev. Biol. 203, 310–319 (1994).

    Article  Google Scholar 

  24. 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 

  25. Cohen, S. M., Brönner, G., Küttner, F., Jürgens, G. & Jäckle, H. Distal-less encodes a homoeodomain protein required for limb development in Drosophila. Nature 338, 432–434 (1989).

    Article  ADS  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  PubMed  Google Scholar 

  27. Hoodless, P. A. et al. MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell 85, 489–500 (1996).

    Article  CAS  Google Scholar 

  28. Wiersdorff, V., Lecuit, T., Cohen, S. M. & Mlodzik, M. Mad acts downstream of the Dpp receptors and reveals differential requirement for dpp signaling between initiation and propagation of morphogenesis in the Drosophila eye. Development 122, 2153–2162 (1996).

    CAS  PubMed  Google Scholar 

  29. Theisen, H., Haerry, T. E., O'Connor, M. B. & Marsh, J. L. Developmental territories created by mutual antagonism between Wingless and Decapentaplegic. Development 122, 3939–3948 (1996).

    CAS  Google Scholar 

  30. Jiang, J. & Struhl, G. Protein kinase A and Hedgehog signaling in Drosophila limb development. Cell 80, 563–572 (1995).

    Article  CAS  Google Scholar 

  31. Lepage, T., Cohen, S. M., Diaz-Benjumea, F. J. & Parkhurst, S. M. Signal transduction by cAMP-dependent protein kinase A in Drosophila limb patterning. Nature 373, 711–715 (1995).

    Article  ADS  CAS  Google Scholar 

  32. Li, W., Ohlmeyer, J. T., Lane, M. E. & Kalderon, D. Function of protein kinase A in Hedgehog signal transduction and Drosophila imaginal disc development. Cell 80, 553–562 (1995).

    Article  CAS  Google Scholar 

  33. Pan, D. J. & Rubin, G. Protein kinase and hedgehog act antagonistically in regulating decapentaplegic transcription in Drosophila imaginal discs. Cell 80, 543–562 (1995).

    Article  CAS  Google Scholar 

  34. Gurdon, J. B., Mitchell, A. & Mahoney, D. Direct and continuous assessment by cells of their position in a morphogen gradient. Nature 376, 520–521 (1995).

    Article  ADS  CAS  Google Scholar 

  35. Gurdon, J. B., Harger, P., Mitchell, A. & Lemaire, P. Activin signalling and response to a morphogen gradient. Nature 371, 487–492 (1994).

    Article  ADS  CAS  Google Scholar 

  36. Riese, J. et al. LEF-1, a nuclear factor coordinating signal inputs from wingless and decapentaplegic. Cell 88, 777–787 (1997).

    Article  CAS  Google Scholar 

  37. Laufer, E., Nelson, C. E., Johnson, R. L., Morgan, B. A. & Tabin, C. Sonic hedgehog and Fgf-4 act through a signalling cascade and feedback loop to integrate growth and patterning of the developing limb bud. Cell 79, 993–1003 (1994).

    Article  CAS  Google Scholar 

  38. Niswander, L., Jeffrey, S., Martin, G. R. & Tickle, C. Apositive feedback loop coordinates growth and patterning of the vertebrate limb. Nature 371, 609–612 (1994).

    Article  ADS  CAS  Google Scholar 

  39. Yang, Y. & Niswander, L. Interaction between the signalling molecules WNT7a and SHH during vertebrate limb development: dorsal signals regulate anteroposterior patterning. Cell 80, 939–947 (1995).

    Article  CAS  Google Scholar 

  40. Crossley, P. H., Minowada, G., MacArthur, C. A. & Martin, G. R. Roles for FGF-8 in the induction, initiation and maintenance of chick limb development. Cell 84, 127–136 (1996).

    Article  CAS  Google Scholar 

  41. Parr, B. A. & McMahon, A. Dorsalizing signal Wnt-7a required for normal polarity of A/P and D/V axes on mouse limb. Nature 374, 350–353 (1995).

    Article  ADS  CAS  Google Scholar 

  42. Niswander, L., Tickle, C., Vogel, A., Booth, I. & Martin, G. R. FGF-4 replaces the apical ectodermal ridge and directs outgrowth and patterning of the limb. Cell 75, 579–587 (1993).

    Article  CAS  Google Scholar 

  43. Cohn, M. J., Izpisua-Belmonte, J. C., Abud, H., Heath, J. K. & Tickle, C. Fibroblast growth factors induce additional limb development fro the flank of chick embryos. Cell 80, 739–746 (1995).

    Article  CAS  Google Scholar 

  44. Ruel, L., Pantesco, V., Lutz, Y., Simpson, P. & Bourouis, M. Functional significance of a family of protein kinases encoded at the shaggy locus in Drosophila. EMBO J. 12, 1657–1669 (1993).

    Article  CAS  Google Scholar 

  45. Vachon, G. et al. Homeotic genes of the Bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene Distal-less. Cell 71, 437–450 (1992).

    Article  CAS  Google Scholar 

  46. Panganiban, G., Sebring, A., Nagy, L. & Carroll, S. B. The development of crustacean limbs and the evolution of arthropods. Science 270, 1363–1366 (1995).

    Article  ADS  CAS  Google Scholar 

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Acknowledgements

We thank G. Struhl, K. Basler and K. Cadigan for fly strains; G. Panganiban and G.Mardon for antibodies; and M. Averof, W. Brook, J. Royet and K. Weigmann for suggestions on the manuscript.

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Correspondence to Stephen M. Cohen.

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Lecuit, T., Cohen, S. Proximal–distal axis formation in the Drosophila leg. Nature 388, 139–145 (1997). https://doi.org/10.1038/40563

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