Theory in Biosciences

, Volume 122, Issue 2–3, pp 288–301 | Cite as

Approaches to a comparison of fin and limb structure and development



Carl Gegenbaur (1865) proposed a specific arrangement of endoskeletal elements as the key feature of a common plan of vertebrate paired appendages which he called the metapterygium. He based the recognition of a metapterygium in different species on endoskeletal pattern but not on its position within the fin/limb. Here I suggest to use the position of Gegenbaur’s metapterygium defined by position of its precursor cells in the fin bud to evaluate homology of metapterygia. The results of developmental studies do not yet bridge the gap between patterning mechanisms and endoskeletal patterns in fins and limbs. Of all genes involved in fin and limb development, the function of Hoxa and Hoxa genes is most closely linked to endoskeleton formation. However, their downstream targets are unknown and it is thus not clear how differences in their expression patterns relate to different skeletal patterns in different species. A comparison of gene function has become possible, however, by the analysis of zebrafish and mouse mutants affecting orthologous genes. Shh and the transcription factor dHand are required for anterior-posterior patterning of fins and limbs. Comparative analysis shows that the initial polarization of the buds involves the action of dHand in both species. Subsequently Shh acts on maintenance and initiation of gene expression along the anterior-posterior axis. Shh maintains developmental progress by interacting with Fgf signalling molecules originating from the ectoderm. However, in spite of general similarities differences exist at the level of Fgf regulation by Shh. In the zebrafish, Shh acts to induce Fgf4 and Fgf8 expression while in the mouse Shh maintains expression of three Fgf genes and Fgf8 expression has escaped Shh regulation. Because Fgfs are important regulators of cell type identity, this difference in Fgf regulation may account for the different proximal-distal extent to which fin and limb buds develop in Shh mutant larvae and pups, respectively.

Key words

zebrafish mouse sonic you sonic hedgehog Fgf 



apical ectodermal maintenance factor


apical ectodermal ridge


zone of polarizing activity


Sonic hedgehog/Fibroblast growth factor gene


Sonic hedgehog/Fibroblast growth factor protein


patched-1/-2 are target genes of Shh


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Balfour, M. (1881) On the development of the skeleton of the paired fins of elasmobranchii, considered in relation to its bearings on the nature of the limbs of vertebrata. Proc Zool Soc London 43: 656–671.Google Scholar
  2. Bouvet, J. (1970) Établissement de la carte des territoires présomptifs du bourgeon de la nageoire pectorale chez la truite indigène (Salmo trutta fario) a l’ aide d’excisions et de marques colorées. Annales d’ Embryologie et de Morphogenèse 3: 315–328.Google Scholar
  3. Charite, J., McFadden, D. G. and Olson, E. N. (2000). The bHLH transcription factor dHAND controls Sonic hedgehog expression and establishment of the zone of polarizing activity during limb development. Development 127: 2461–2470.PubMedGoogle Scholar
  4. Chiang, C., Litingtung, Y., Harris, M. P., Simandl, B. K., Li, Y., Beachy, P. A. and Fallon, J. F. (2001) Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function. Dev Biol 236: 421–435.PubMedCrossRefGoogle Scholar
  5. Chiang, C., Litingtung, Y., Lee, E., Young, K. E., Corden, J. L., Westphal, H. and Beachy, P. A. (1996) Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383: 407–413.PubMedCrossRefGoogle Scholar
  6. Coates, M. I. (1994) The origin of vertebrate limbs. Dev Suppl, 169–180.Google Scholar
  7. Coates, M. I. (1995) Limb evolution. Fish fins or tetrapod limbs — a simple twist of fate? Curr Biol 5: 844–848.PubMedCrossRefGoogle Scholar
  8. Davis, A. P., Witte, D. P., Hsieh-Li, H. M., Potter, S. S. and Capecchi, M. R. (1995) Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. Nature 375: 791–795.PubMedCrossRefGoogle Scholar
  9. Duboule, D. (1994) How to make a limb? Science 266: 575–576.PubMedCrossRefGoogle Scholar
  10. Duboule, D. (1995) Vertebrate Hox genes and proliferation: an alternative pathway to homeosis? Curr Opin Genet Dev 5: 525–528.PubMedCrossRefGoogle Scholar
  11. Fernandez-Teran, M., Piedra, M. E., Kathiriya, I. S., Srivastava, D., Rodriguez-Rey, J. C. and Ros, M. A. (2000) Role of dHAND in the anterior-posterior polarization of the limb bud: implications for the Sonic hedgehog pathway. Development 127: 2133–2142.PubMedGoogle Scholar
  12. Fromental-Ramain, C., Warot, X., Messadecq, N., LeMeur, M., Dolle, P. and Chambon, P. (1996) Hoxa-13 and Hoxd-13 play a crucial role in the patterning of the limb autopod. Development 122: 2997–3011.PubMedGoogle Scholar
  13. Gegenbaur, C. (1865) Untersuchungen zur vergleichenden Anatomie der Wirbeltiere. Vol. II. Leipzig: Wilhelm Engelmann.Google Scholar
  14. Gegenbaur, C. (1870) Über das Skelett der Gliedmassen der Wirbeltiere im Allgemeinen und der Hintergliedmassen der Selachier insbesondere. Jena Z. Naturw. 5: 397–447.Google Scholar
  15. Gegenbaur, C. (1872) Über das Archipterygium. Jena Z. Naturw. 7: 131–141.Google Scholar
  16. Gegenbaur, C. (1876) Zur Morphologie der Gliedmassen der Wirbeltiere. Morph. Jarhb. 2: 396–420.Google Scholar
  17. Goodrich, E. (1930) Studies on the structure and development of vertebrates. Chicago, IL.: The Uiversity of Chicago Press.Google Scholar
  18. Grandel, H., Draper, B. W. and Schulte-Merker, S. (2000) dackel acts in the ectoderm of the zebrafish pectoral fin bud to maintain AER signaling. Development 127: 4169–4178.PubMedGoogle Scholar
  19. Grandel, H. and Schulte-Merker, S. (1998) The development of the paired fins in the zebrafish (Danio rerio). Mech Dev 79: 99–120.PubMedCrossRefGoogle Scholar
  20. Heronimus, C. (1911) Die Entwicklung des Brustflossenskelettes bei Amia calva. Anatomischer Anzeiger 34: 193–203.Google Scholar
  21. Jessen, H. (1972) Schultergürtel und Pectoralflosse bei Actinopterygiern. Oslo: Universitetsforlaget Oslo.Google Scholar
  22. Kraus, P., Fraidenraich, D. and Loomis, C. A. (2001) Some distal limb structures develop in mice lacking Sonic hedgehog signaling. Mech Dev 100: 45–58.PubMedCrossRefGoogle Scholar
  23. Krauss, S., Concordet, J. P. and Ingham, P. W. (1993) A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell 75: 1431–1444.PubMedCrossRefGoogle Scholar
  24. Laufer, E., Nelson, C. E., Johnson, R. L., Morgan, B. A. and Tabin, C. (1994) Sonic hedgehog and Fgf-4 act through a signaling cascade and feedback loop to integrate growth and patterning of the developing limb bud. Cell 79: 993–1003.PubMedCrossRefGoogle Scholar
  25. Litingtung, Y., Dahn, R.D., Li Y., Fallon, J.F., Chiang, C. (2002) Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity. Nature 418: 979–983.PubMedCrossRefGoogle Scholar
  26. Mabee, P. (2000) Developmental data and phylogenetic systematics: evolution of the vertebrate limb. American Zoologist 40: 789–800.CrossRefGoogle Scholar
  27. Martin, G. R. (1998) The roles of FGFs in the early development of vertebrate limbs. Genes Dev 12: 1571–1586.PubMedGoogle Scholar
  28. Martin, G. (2001) Making a vertebrate limb: new players enter from the wings. Bioessays 23: 865–868.PubMedCrossRefGoogle Scholar
  29. Morgan, B. A., Izpisua-Belmonte, J. C., Duboule, D. and Tabin, C. J. (1992) Targeted misexpression of Hox-4.6 in the avian limb bud causes apparent homeotic transformations. Nature 358: 236–239.PubMedCrossRefGoogle Scholar
  30. Neumann, C. J., Grandel, H., Gaffield, W., Schulte-Merker, S. and Nüsslein-Volhard, C. (1999) Transient establishment of anteroposterior polarity in the zebrafish pectoral fin bud in the absence of sonic hedgehog activity. Development 126: 4817–4826.PubMedGoogle Scholar
  31. Niswander, L., Jeffrey, S., Martin, G. R. and Tickle, C. (1994) A positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature 371: 609–612.PubMedCrossRefGoogle Scholar
  32. Ohuchi, H., Nakagawa, T., Yamamoto, A., Araga, A., Ohata, T., Ishimaru, Y., Yoshioka, H., Kuwana, T., Nohno, T., Yamasaki, M. et al. (1997) The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor. Development 124: 2235–2244.PubMedGoogle Scholar
  33. Pearse, R. V., 2nd and Tabin, C. J. (1998) The molecular ZPA. J Exp Zool 282: 677–690.PubMedCrossRefGoogle Scholar
  34. Reifers, F., Böhli, H., Walsh, E. C., Crossley, P. H., Stainier, D. Y. R. and Brand, M. (1998) Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and somitogenesis. Development 125: 2381–2395.PubMedGoogle Scholar
  35. Riddle, R. D., Johnson, R. L., Laufer, E. and Tabin, C. (1993) Sonic hedgehog mediates the polarizzing activity of the ZPA. Cell 75: 1401–1416.PubMedCrossRefGoogle Scholar
  36. Saunders, J. W. (1948) the proximo-distal sequence of origin of the parts of the chick wing and the role of the ectoderm. J Exp Zool 108: 363–403.CrossRefGoogle Scholar
  37. Saunders, J. W. and Gasseling, M. T. (1968) Ectodermal-mesenchymal interactions in the origin of limb symmetry. Baltimore: Williams and Wilkins.Google Scholar
  38. Sewertzoff, A. (1926) Die Morphologie der Brustflossen der Fische. Jenaische Zeitschrift für Naturwissenschaften 62: 343–392.Google Scholar
  39. Shubin, N. (1995) The evolution of paired fins and the origin of tetrapod limbs. Evolutionary Biology 28: 39–86.Google Scholar
  40. Sordino, P., van der Hoeven, F. and Duboule, D. (1995) Hox gene expression in teleost fins and the origin of vertebrate digits. Nature 375: 678–681.PubMedCrossRefGoogle Scholar
  41. Sordino, P. and Duboule, D. (1996) A molecular approach to the evolution of vertebrate paired appendages. TREE 11: 114–119.Google Scholar
  42. Sun, X., Mariani, F. V. and Martin, G. R. (2002) Functions of FGF signalling from the apical ectodermal ridge in limb development. Nature 418: 501–508.PubMedCrossRefGoogle Scholar
  43. Tabin, C. J. (1992) Why we have (only) five fingers per hand: hox genes and the evolution of paired limbs. Development 116: 289–296.PubMedGoogle Scholar
  44. Tanaka, M., Münsterberg, A., Anerson, W. G., Prescott, A. R., Hazon, N., Tickle, C. (2002) Fin development in a cartilaginous fish and the origin of vertebrate limbs. Nature 416: 527–531.PubMedCrossRefGoogle Scholar
  45. te Welscher, P., Fernandez-Teran, M., Ros, M. A. and Zeller, R. (2002a) Mutual genetic antagonism involving GLI3 and dHAND prepatterns the vertebrate limb bud mesenchyme prior to SHH signaling. Genes Dev 16: 421–426.CrossRefGoogle Scholar
  46. te Welscher, P., Zuniga, A., Kuijper, S., Drenth, T., Goedemans, H. J., Meijlink, F., Zeller, R. (2002b) Progression of vertebrate limb development through Shh-mediated Counteraction of Gli3. Science 298: 827–830.CrossRefGoogle Scholar
  47. Tickle, C., Summerbell, D. and Wolpert, L. (1975) Positional signalling and specification of digits in chick limb morphogenesis. Nature 254, 199–202.PubMedCrossRefGoogle Scholar
  48. Vogel, A. and Tickle, C. (1993). FGF-4 maintains polarizing activity of posterior limb bud cells in vivo and in vitro. Development 119: 199–206.PubMedGoogle Scholar
  49. Vogel, A., Rodriguez, C. and Izpisua-Belmonte, J. C. (1996) Involvement of FGF-8 in initiation, outgrowth and patterning of the vertebrate limb. Development 122: 1737–1750.PubMedGoogle Scholar
  50. Yelon, D., Ticho, B., Halpern, M. E., Ruvinsky, I., Ho, R. K., Silver, L. M. and Stainier, D. Y. (2000) The bHLH transcription factor hand2 plays parallel roles in zebrafish heart and pectoral fin development. Development 127: 2573–2582.PubMedGoogle Scholar
  51. Zangerl, R. (1981) Handbook of Paleoichthyology, Chondrichthyes I. Stuttgart New York: Gustav Fischer Verlag.Google Scholar
  52. Zúñiga, A., Haramis, A. P., McMahon, A. P. and Zeller, R. (1999) Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds. Nature 401: 598–602.PubMedCrossRefGoogle Scholar
  53. Zúñiga, A. and Zeller, R. (1999) Gli3 (Xt) and formin (ld) participate in the positioning of the polarising region and control of posterior limb-bud identity. Development 126: 13–21.PubMedGoogle Scholar
  54. Zwilling, E. (1961) Limb morphogenesis. Advances in Morphogenesis 1: 301–330.Google Scholar

Copyright information

© Urban & Fischer Verlag 2003

Authors and Affiliations

  1. 1.Max-Planck-Institut für molekulare Zellbiologie und GenetikDresdenGermany

Personalised recommendations