Skip to main content
PMC home page
Journal of Anatomy logoLink to Journal of Anatomy
. 2001 Jul-Aug;199(Pt 1-2):195–204. doi: 10.1046/j.1469-7580.2001.19910195.x

Evolutionary aspects of positioning and identification of vertebrate limbs

KOJI TAMURA 1 ,✉, RITSU KURAISHI 2 , DAISUKE SAITO 1 , HIDEKI MASAKI 1 , HIROYUKI IDE 1 , SAYURI YONEI-TAMURA 1
PMCID: PMC1594969  PMID: 11523823

Abstract

Emerging developmental studies contribute to our understanding of vertebrate evolution because changes in the developmental process and the genes responsible for such changes provide a unique way for evaluating the evolution of morphology. Endoskeletal limbs, the locomotor organs that are unique to vertebrates, are a popular model system in the fields of palaeontology and phylogeny because their structure is highly visible and their bony pattern is easily preserved in the fossil records. Similarly, limb development has long served as an excellent model system for studying vertebrate pattern formation. In this review, the evolution of vertebrate limb development is examined in the light of the latest knowledge, viewpoints and hypotheses.

Keywords: Limb, limb bud, development, vertebrate, evolution, AER, FGF, Tbx

Full Text

The Full Text of this article is available as a PDF (463.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abud H. E., Skinner J. A., McDonald F. J., Bedford M. T., Lonai P., Heath J. K. Ectopic expression of Fgf-4 in chimeric mouse embryos induces the expression of early markers of limb development in the lateral ridge. Dev Genet. 1996;19(1):51–65. doi: 10.1002/(SICI)1520-6408(1996)19:1<51::AID-DVG6>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
  2. Agulnik S. I., Garvey N., Hancock S., Ruvinsky I., Chapman D. L., Agulnik I., Bollag R., Papaioannou V., Silver L. M. Evolution of mouse T-box genes by tandem duplication and cluster dispersion. Genetics. 1996 Sep;144(1):249–254. doi: 10.1093/genetics/144.1.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Akimenko M. A., Ekker M. Anterior duplication of the Sonic hedgehog expression pattern in the pectoral fin buds of zebrafish treated with retinoic acid. Dev Biol. 1995 Jul;170(1):243–247. doi: 10.1006/dbio.1995.1211. [DOI] [PubMed] [Google Scholar]
  4. Basson C. T., Bachinsky D. R., Lin R. C., Levi T., Elkins J. A., Soults J., Grayzel D., Kroumpouzou E., Traill T. A., Leblanc-Straceski J. Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome. Nat Genet. 1997 Jan;15(1):30–35. doi: 10.1038/ng0197-30. [DOI] [PubMed] [Google Scholar]
  5. Carrington J. L., Fallon J. F. The stages of flank ectoderm capable of responding to ridge induction in the chick embryo. J Embryol Exp Morphol. 1984 Dec;84:19–34. [PubMed] [Google Scholar]
  6. Chapman D. L., Garvey N., Hancock S., Alexiou M., Agulnik S. I., Gibson-Brown J. J., Cebra-Thomas J., Bollag R. J., Silver L. M., Papaioannou V. E. Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development. Dev Dyn. 1996 Aug;206(4):379–390. doi: 10.1002/(SICI)1097-0177(199608)206:4<379::AID-AJA4>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
  7. Coates M. I. The origin of vertebrate limbs. Dev Suppl. 1994:169–180. [PubMed] [Google Scholar]
  8. Cohn M. J., Izpisúa-Belmonte J. C., Abud H., Heath J. K., Tickle C. Fibroblast growth factors induce additional limb development from the flank of chick embryos. Cell. 1995 Mar 10;80(5):739–746. doi: 10.1016/0092-8674(95)90352-6. [DOI] [PubMed] [Google Scholar]
  9. Crossley P. H., Minowada G., MacArthur C. A., Martin G. R. Roles for FGF8 in the induction, initiation, and maintenance of chick limb development. Cell. 1996 Jan 12;84(1):127–136. doi: 10.1016/s0092-8674(00)80999-x. [DOI] [PubMed] [Google Scholar]
  10. Echelard Y., Epstein D. J., St-Jacques B., Shen L., Mohler J., McMahon J. A., McMahon A. P. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 1993 Dec 31;75(7):1417–1430. doi: 10.1016/0092-8674(93)90627-3. [DOI] [PubMed] [Google Scholar]
  11. Endo T., Yokoyama H., Tamura K., Ide H. Shh expression in developing and regenerating limb buds of Xenopus laevis. Dev Dyn. 1997 Jun;209(2):227–232. doi: 10.1002/(SICI)1097-0177(199706)209:2<227::AID-AJA8>3.0.CO;2-K. [DOI] [PubMed] [Google Scholar]
  12. Fallon J. F., López A., Ros M. A., Savage M. P., Olwin B. B., Simandl B. K. FGF-2: apical ectodermal ridge growth signal for chick limb development. Science. 1994 Apr 1;264(5155):104–107. doi: 10.1126/science.7908145. [DOI] [PubMed] [Google Scholar]
  13. Gibson-Brown J. J., Agulnik S. I., Chapman D. L., Alexiou M., Garvey N., Silver L. M., Papaioannou V. E. Evidence of a role for T-box genes in the evolution of limb morphogenesis and the specification of forelimb/hindlimb identity. Mech Dev. 1996 May;56(1-2):93–101. doi: 10.1016/0925-4773(96)00514-x. [DOI] [PubMed] [Google Scholar]
  14. Gibson-Brown J. J., Agulnik S. I., Silver L. M., Niswander L., Papaioannou V. E. Involvement of T-box genes Tbx2-Tbx5 in vertebrate limb specification and development. Development. 1998 Jul;125(13):2499–2509. doi: 10.1242/dev.125.13.2499. [DOI] [PubMed] [Google Scholar]
  15. Igarashi M., Finch P. W., Aaronson S. A. Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7). J Biol Chem. 1998 May 22;273(21):13230–13235. doi: 10.1074/jbc.273.21.13230. [DOI] [PubMed] [Google Scholar]
  16. Imokawa Y., Yoshizato K. Expression of Sonic hedgehog gene in regenerating newt limb blastemas recapitulates that in developing limb buds. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9159–9164. doi: 10.1073/pnas.94.17.9159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Isaac A., Rodriguez-Esteban C., Ryan A., Altabef M., Tsukui T., Patel K., Tickle C., Izpisúa-Belmonte J. C. Tbx genes and limb identity in chick embryo development. Development. 1998 May;125(10):1867–1875. doi: 10.1242/dev.125.10.1867. [DOI] [PubMed] [Google Scholar]
  18. Li Q. Y., Newbury-Ecob R. A., Terrett J. A., Wilson D. I., Curtis A. R., Yi C. H., Gebuhr T., Bullen P. J., Robson S. C., Strachan T. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat Genet. 1997 Jan;15(1):21–29. doi: 10.1038/ng0197-21. [DOI] [PubMed] [Google Scholar]
  19. Logan M., Simon H. G., Tabin C. Differential regulation of T-box and homeobox transcription factors suggests roles in controlling chick limb-type identity. Development. 1998 Aug;125(15):2825–2835. doi: 10.1242/dev.125.15.2825. [DOI] [PubMed] [Google Scholar]
  20. 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. 1993 Nov 5;75(3):579–587. doi: 10.1016/0092-8674(93)90391-3. [DOI] [PubMed] [Google Scholar]
  21. Ohuchi H., Nakagawa T., Yamamoto A., Araga A., Ohata T., Ishimaru Y., Yoshioka H., Kuwana T., Nohno T., Yamasaki M. The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor. Development. 1997 Jun;124(11):2235–2244. doi: 10.1242/dev.124.11.2235. [DOI] [PubMed] [Google Scholar]
  22. Ohuchi H., Nakagawa T., Yamauchi M., Ohata T., Yoshioka H., Kuwana T., Mima T., Mikawa T., Nohno T., Noji S. An additional limb can be induced from the flank of the chick embryo by FGF4. Biochem Biophys Res Commun. 1995 Apr 26;209(3):809–816. doi: 10.1006/bbrc.1995.1572. [DOI] [PubMed] [Google Scholar]
  23. Ohuchi H., Takeuchi J., Yoshioka H., Ishimaru Y., Ogura K., Takahashi N., Ogura T., Noji S. Correlation of wing-leg identity in ectopic FGF-induced chimeric limbs with the differential expression of chick Tbx5 and Tbx4. Development. 1998 Jan;125(1):51–60. doi: 10.1242/dev.125.1.51. [DOI] [PubMed] [Google Scholar]
  24. Papaioannou V. E., Silver L. M. The T-box gene family. Bioessays. 1998 Jan;20(1):9–19. doi: 10.1002/(SICI)1521-1878(199801)20:1<9::AID-BIES4>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  25. Riddle R. D., Johnson R. L., Laufer E., Tabin C. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell. 1993 Dec 31;75(7):1401–1416. doi: 10.1016/0092-8674(93)90626-2. [DOI] [PubMed] [Google Scholar]
  26. Rodriguez-Esteban C., Tsukui T., Yonei S., Magallon J., Tamura K., Izpisua Belmonte J. C. The T-box genes Tbx4 and Tbx5 regulate limb outgrowth and identity. Nature. 1999 Apr 29;398(6730):814–818. doi: 10.1038/19769. [DOI] [PubMed] [Google Scholar]
  27. Ruvinsky I., Gibson-Brown J. J. Genetic and developmental bases of serial homology in vertebrate limb evolution. Development. 2000 Dec;127(24):5233–5244. doi: 10.1242/dev.127.24.5233. [DOI] [PubMed] [Google Scholar]
  28. Ruvinsky I., Oates A. C., Silver L. M., Ho R. K. The evolution of paired appendages in vertebrates: T-box genes in the zebrafish. Dev Genes Evol. 2000 Feb;210(2):82–91. doi: 10.1007/s004270050014. [DOI] [PubMed] [Google Scholar]
  29. Saunders J. W., Jr, Reuss C. Inductive and axial properties of prospective wing-bud mesoderm in the chick embryo. Dev Biol. 1974 May;38(1):41–50. doi: 10.1016/0012-1606(74)90257-7. [DOI] [PubMed] [Google Scholar]
  30. Searls R. L., Janners M. Y. The initiation of limb bud outgrowth in the embryonic chick. Dev Biol. 1971 Feb;24(2):198–213. doi: 10.1016/0012-1606(71)90095-9. [DOI] [PubMed] [Google Scholar]
  31. Sekine K., Ohuchi H., Fujiwara M., Yamasaki M., Yoshizawa T., Sato T., Yagishita N., Matsui D., Koga Y., Itoh N. Fgf10 is essential for limb and lung formation. Nat Genet. 1999 Jan;21(1):138–141. doi: 10.1038/5096. [DOI] [PubMed] [Google Scholar]
  32. Simon H. G., Kittappa R., Khan P. A., Tsilfidis C., Liversage R. A., Oppenheimer S. A novel family of T-box genes in urodele amphibian limb development and regeneration: candidate genes involved in vertebrate forelimb/hindlimb patterning. Development. 1997 Apr;124(7):1355–1366. doi: 10.1242/dev.124.7.1355. [DOI] [PubMed] [Google Scholar]
  33. Stephens T. D., Beier R. L., Bringhurst D. C., Hiatt S. R., Prestridge M., Pugmire D. E., Willis H. J. Limbness in the early chick embryo lateral plate. Dev Biol. 1989 May;133(1):1–7. doi: 10.1016/0012-1606(89)90290-x. [DOI] [PubMed] [Google Scholar]
  34. Tabin C. J. Why we have (only) five fingers per hand: hox genes and the evolution of paired limbs. Development. 1992 Oct;116(2):289–296. doi: 10.1242/dev.116.2.289. [DOI] [PubMed] [Google Scholar]
  35. Takabatake Y., Takabatake T., Takeshima K. Conserved and divergent expression of T-box genes Tbx2-Tbx5 in Xenopus. Mech Dev. 2000 Mar 1;91(1-2):433–437. doi: 10.1016/s0925-4773(99)00329-9. [DOI] [PubMed] [Google Scholar]
  36. Takeuchi J. K., Koshiba-Takeuchi K., Matsumoto K., Vogel-Höpker A., Naitoh-Matsuo M., Ogura K., Takahashi N., Yasuda K., Ogura T. Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds. Nature. 1999 Apr 29;398(6730):810–814. doi: 10.1038/19762. [DOI] [PubMed] [Google Scholar]
  37. Tamura K., Yonei-Tamura S., Izpisúa Belmonte J. C. Differential expression of Tbx4 and Tbx5 in Zebrafish fin buds. Mech Dev. 1999 Sep;87(1-2):181–184. doi: 10.1016/s0925-4773(99)00126-4. [DOI] [PubMed] [Google Scholar]
  38. Tanaka M., Cohn M. J., Ashby P., Davey M., Martin P., Tickle C. Distribution of polarizing activity and potential for limb formation in mouse and chick embryos and possible relationships to polydactyly. Development. 2000 Sep;127(18):4011–4021. doi: 10.1242/dev.127.18.4011. [DOI] [PubMed] [Google Scholar]
  39. Torok M. A., Gardiner D. M., Izpisúa-Belmonte J. C., Bryant S. V. Sonic hedgehog (shh) expression in developing and regenerating axolotl limbs. J Exp Zool. 1999 Jul 1;284(2):197–206. [PubMed] [Google Scholar]
  40. Vogel A., Rodriguez C., Izpisúa-Belmonte J. C. Involvement of FGF-8 in initiation, outgrowth and patterning of the vertebrate limb. Development. 1996 Jun;122(6):1737–1750. doi: 10.1242/dev.122.6.1737. [DOI] [PubMed] [Google Scholar]
  41. Yokoyama H., Ide H., Tamura K. FGF-10 stimulates limb regeneration ability in Xenopus laevis. Dev Biol. 2001 May 1;233(1):72–79. doi: 10.1006/dbio.2001.0180. [DOI] [PubMed] [Google Scholar]
  42. Yokoyama H., Yonei-Tamura S., Endo T., Izpisúa Belmonte J. C., Tamura K., Ide H. Mesenchyme with fgf-10 expression is responsible for regenerative capacity in Xenopus limb buds. Dev Biol. 2000 Mar 1;219(1):18–29. doi: 10.1006/dbio.1999.9587. [DOI] [PubMed] [Google Scholar]
  43. Yonei-Tamura S., Endo T., Yajima H., Ohuchi H., Ide H., Tamura K. FGF7 and FGF10 directly induce the apical ectodermal ridge in chick embryos. Dev Biol. 1999 Jul 1;211(1):133–143. doi: 10.1006/dbio.1999.9290. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Anatomy are provided here courtesy of Anatomical Society of Great Britain and Ireland

RESOURCES