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The Role of Retinoic Acid in Vertebrate Limb Morphogenesis

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Part of the book series: NATO ASI Series ((NSSA,volume 195))

Abstract

How an organism develops from a fertilized egg is one of the most challenging questions in biology, and accordingly, has interested biologists for a very long time. Recent advances in molecular and cellular techniques have provided useful tools that are now applied to many of the basic questions of embryology. For example, how do cells during embryogenesis form the intricate spatial pattern of tissues characteristic for an organism, and how does the broad spectrum of differentiated cell types arise during embryonic development? It is widely appreciated that pattern formation and cell differentiation depend on a concerted expression of specific genes and in many cases also on cell-cell interactions. For example, in Caenorhabditis elegans two genes that specify cell fate (lin-12 and glp-l) encode receptor-like transmembrane proteins whose extracellular domains share structural similarities with a diffusible ligand such as epidermal growth factor (for a review see Greenwald, 1989). In Drosophila, there is also good evidence that intercellular communication is operative in pattern formation e.g. of the epidermis (reviewed by Arias, 1989) and of the retina (reviewed by Rubin, 1989).

In my possession are two little embryos in spirit, whose names I have omitted to attach, and at present I am quite unable to say to what class they belong. They may be lizards or small birds, or very young mammalia, so complete is the similarity in the mode of formation of the head and trunk in these animals. The extremities, however, are still absent in these embryos. But even if they had existed in the earliest stages of their development we should learn nothing, for the feet of lizards and mammals, the wings and feet of birds, no less than the hands and feet of man, all arise from the same fundamental form.

K. von Baer, quoted in Darwin (1859)

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References

  • Arias, A.M., 1989, A cellular basis for pattern formation in the insect epidermis, Trends Genet., 5: 262.

    Article  Google Scholar 

  • Balling, R., Mutter, G., Gruss, P., and Kessel, M., 1989, Craniofacial abnormalities induced by ectopic expression of homeobox gene Hox-1.1 in transgenic mice, Cell, 58: 337.

    Article  PubMed  CAS  Google Scholar 

  • Beato, M., 1989, Gene regulation by steroid hormone, Cell, 56: 335.

    Article  PubMed  CAS  Google Scholar 

  • Benbrook, D., Lernhardt, E., and Pfahl, M., 1988, A new retinoic acid receptor identified from rat hepatocellular carcinoma, Nature (Lond.), 333: 669.

    Article  CAS  Google Scholar 

  • Brand, N.J., Petkovich, M., Krust, A. and Chambon, P., de Thé, H., Marchio, A, Tiollais, P., and Dejean, A., 1988, Identification of a second human retinoic acid receptor, Nature, 332: 850.

    Article  PubMed  CAS  Google Scholar 

  • Brockes, J.P., 1989, Retinoids, homeobox genes, and limb morphogenesis, Neuron, 2: 1285.

    Article  PubMed  CAS  Google Scholar 

  • Bryant, S.V., French, V., Bryant, P.J., 1981, Distal regeneration and symmetry, Science, 212: 993.

    Article  PubMed  CAS  Google Scholar 

  • Bryant, S.,V., and Muneoka, K., 1986, Views of limb development and regeneration, Trends Genet., 2: 153.

    Article  Google Scholar 

  • Christ, B., Jacob, H.J., and Jacob, M., 1977, Experimental analysis of the origin of the wing musculature in avian embryos, Anat. Embryol., 150: 171.

    Article  PubMed  CAS  Google Scholar 

  • Chytil, F., and Ong, D.E., 1984, Cellular Retinoid-binding Proteins in: “The Retinoids,” M.B. Sporn, A.B. Roberts, and D.S. Goodman, eds., Academic Press, Orlando, (vol.2), pp. 89–123

    Google Scholar 

  • Cooke, J. and Summerbell, D., 1980, Cell cycle and experimental pattern duplication in the chick wing during embryonic development, Nature (Lond.), 287: 697.

    Article  CAS  Google Scholar 

  • Darwin, C., 1859, “On The Origin of Species by Means of Natural Selection, or the Preservation of Favored Races in the Struggle for Life,” Murray, London,

    Google Scholar 

  • de The, H., Marchio, A., Tiollais, P., and Dejean, A., 1989, Differential expression and ligand regulation of the retinoic acid receptor alpha and beta genes, EMBO J., 8: 429.

    PubMed  Google Scholar 

  • Douer, D, and Koeffler, H.P., 1982, Inhibition of clonal growth of human myeloid leukemia cells, J. Clin. Invest., 69: 277.

    Article  PubMed  CAS  Google Scholar 

  • Dowling, J.E., and Wald, G., 1960, The biological function of vitamin A acid, Proc. Natl. Acad. Sci., 46: 587.

    Article  PubMed  CAS  Google Scholar 

  • Eichele, G., 1989, Retinoids and vertebrate limb pattern formation, Trends Genet., 5: 246.

    Article  PubMed  CAS  Google Scholar 

  • Eichele, G., Tickle, C., and Alberts, B.M., 1985, Studies on the mechanism of retinoid-induced pattern duplications in the early chick limb bud: temporal and spatial aspects, J. Cell Biol., 101: 1913.

    Article  PubMed  CAS  Google Scholar 

  • Eichele, G., and Thaller, C., 1987, Characterization of concentration gradients of a morphogenetically active retinoid in the chick limb bud, J. Cell Biol., 105: 1917.

    Article  PubMed  CAS  Google Scholar 

  • Evans, R.M., 1988, The steroid and thyroid hormone receptor super-family, Science, 240: 889.

    Article  PubMed  CAS  Google Scholar 

  • Fallon, J.F., Rowe, D.A., Frederick, J.M., and Simandl, B.K., 1983, Studies on epithelial-mesenchymal interactions during limb development in: “Epithelial-mesenchymal Interactions in Development,” R.H. Sawyer and J.F. Fallon, eds., Praeger Scientific, New York, pp. 3–25.

    Google Scholar 

  • Gehring, W.J., 1987, Homeo boxes in the study of development, Science, 236: 1245.

    Article  PubMed  CAS  Google Scholar 

  • Gelbart, W.M., Irish, V.F., St., Johnston, R.D., Hoffmann, F.M., Blackman, R.K., Segal, D., Posakony, L.M., and Grimalia, R., 1985, The decapentaplegic gene complex in Drosophila melanogaster, Cold Spring Habor Symp. Quant. Biol., 50: 119.

    Article  CAS  Google Scholar 

  • Giguère, V., Ong, E.S., Segui, P., and Evans, R.M., 1987, Identification of a receptor for the morphogen retinoic acid, Nature (Lond.), 330: 624.

    Article  Google Scholar 

  • Giguère, V., Ong, E.S., Evans, R.M., and Tabin, C., 1989, Spatial and temporal expression of the retinoic acid receptor in the regenerating amphibian limb, Nature (Lond.), 337: 714.

    Article  Google Scholar 

  • Green, S., and Chambon, P., (1988), Nuclar receptors enhance our understanding of transcriptional regulation, Trends Genet., 4: 309.

    Article  PubMed  CAS  Google Scholar 

  • Greenwald, I., 1989, Cell-cell interactions that specify cell fates in C. elegans in development, Trends Genet., 5: 237.

    Article  PubMed  CAS  Google Scholar 

  • Gumpel-Pinot, M., 1974, Contribution du mésoderme somitique à la genèse du membre chez l’embryon d’oiseau, C.r.hebd. Séanc. Acad. Sci. Paris D, 279: 1305.

    CAS  Google Scholar 

  • Hamburger, V., and Hamilton, H., 1951, A series of normal stages in the development of the chick embryo, J. Morph., 88: 49.

    Article  Google Scholar 

  • Hinchliffe, J.R., and Johnson, D.R., 1980, “The Development of the Vertebrate Limb,” Clarendon Press, Oxford.

    Google Scholar 

  • Holland P. W. H., and Hogan, B. L. M., 1988, Expression of homeobox genes during mouse development: a review, Genes Dev., 2: 773.

    Article  PubMed  CAS  Google Scholar 

  • Hooper, M., Hardy, K., Handyside, A., Hunter, S., and Monk, M., 1987, HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germ line colonization by cultured cells, Nature (Lond.), 326: 292.

    Article  CAS  Google Scholar 

  • Honig, L.S., 1984, Pattern formation during development of the amniote limb in: “The Structure, Development and Evolution of Reptiles,” M.W.J. Ferguson, ed., Academic Press, London, pp. 197–221.

    Google Scholar 

  • Jaenisch, R., 1988, Transgenic animals, Science, 240: 1468.

    Article  PubMed  CAS  Google Scholar 

  • Kelley, R.O., and Fallon, J.F., 1981, The developing limb: an analysis of interacting cells and tissues in a model morphogenetic system in; “Morphogenesis and Pattern Formation,” T.G. Connelly et al., eds., Raven Press, New York, pp. 4 9–85.

    Google Scholar 

  • Kochhar, D.M., 1977, Abnormal organogenesis in the limb in: Handbook of Teratology,” J.G. Wilson, and F.C. Fraser, eds., Plenum Press, New York, pp. 453–479.

    Google Scholar 

  • Krust, A., Kastner, P., Petkovich, M., Zelent, A., and Chambon, P., 1989, A third human retinoic acid receptor, hRARγ, Proc. Natl. Acad. Sci., 86: 5310.

    Article  PubMed  CAS  Google Scholar 

  • Kuehn, M.R., Bradley, A., Robertson, E.J., and Evans, M.J., 1987, A potential animal model for Lesch-Nyhan syndrome trough introduction of HPRT mutations into mice, Nature, 326: 295.

    Article  PubMed  CAS  Google Scholar 

  • Kuner, J.M., Nakanishi, M., Ali, Ζ., Drees, B., Gustavson, E., Theis, J., Kauvar, L., komberg, T., and O’Farrell, P.H., 1985, Molecular cloning of engrailed: A gene involved in development of pattern in Drosophila melanogaster, Cell, 42: 309.

    Article  CAS  Google Scholar 

  • Lewis, J.H., 1975, Fate maps and the attern of cell division: a calculation for the chick wing bud, J. Embryol, exp. Morph., 33: 419.

    CAS  Google Scholar 

  • Maden, M., Ong, D.E., Summerbell, D., and Chytil, F., 1988, Spatial distribution of cellular protein binding to retinoic acid in the chick limb bud, Nature (Lond.), 335: 733.

    Article  CAS  Google Scholar 

  • McGinnis, W., Garber, R.L., Wirz, J., Kuroiwa, A., and Gehring, W., 1984, A homologous protein coding sequence in Drosophila homeotic genes and its conservation in other metazoans, Cell, 37: 403.

    Article  PubMed  CAS  Google Scholar 

  • McMahon, A.P., and Moon, R.T., 1989, Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis, Cell, 58: 1075.

    Article  PubMed  CAS  Google Scholar 

  • Newman, S.A., 1988, Lineage and pattern in the developing vertebrate limb, Trends Genet., 4: 329.

    Article  PubMed  CAS  Google Scholar 

  • O’Rahilly, R., and Gardener, E., 1975, The timing and sequence of the limbs in the human embryo, Anat. Embryol., 148: 1.

    Article  PubMed  Google Scholar 

  • Patou, M.P., 1977, Dorso-ventral axis determination of chick limb bud development in: “Vertebrate Limb and Somite Morphogenesis,” D.A. Ede, J.R. Hinchliffe, and M. Balls, eds., University Press, Cambridge, pp. 257–266.

    Google Scholar 

  • Peifer, M., Krach, F., and Bender, W., 1988, The bithorax complex: control and segmental identity, Genes Dev., 1: 891.

    Article  Google Scholar 

  • Petkovich, M., Brand, N.J., Krust, A., and Chambon, P., 1987, A human retinoic acid receptor which belongs to the family of nuclear receptors, Nature (Lond.), 330: 444.

    Article  CAS  Google Scholar 

  • Ragsdale, C.W., Petkovich, M., Gates, P.B., Chambon, P., and Brokes, J.P., 1989, Indentification of a novel retinoic acid receptor in regenerative tissues of the newt, Nature (Lond.), 341: 654.

    Article  CAS  Google Scholar 

  • Raynaud, A., 1985, Development of limbs and embryonic limb reduction in: “Biology of Reptilia,” C. Gans and F. Billett, eds., Wiley & Sons, New York, pp. 60–148.

    Google Scholar 

  • Rosa, F.M., 1989, Mix.1 a homeobox mRNA inducible by mesoderm inducers, is expressed mostly in the presumptive endodermal cells of Xenopus embryos, Cell, 57: 965.

    Article  PubMed  CAS  Google Scholar 

  • Rubin, G.M., 1989, Development of Drosophila retina: inductive events studied at single cell resolution, Cell, 57: 519.

    Article  PubMed  CAS  Google Scholar 

  • Sasse, J. Horwitz, A., Pacifici, M., and Holtzer, H., 1984, Separation of precursor myogenic and chondrogenic cells in early limb bud mesenchyme by a monoclonal antibody, J. Cell Biol., 99: 1856.

    Google Scholar 

  • Sassoon, D., Lyons, G., Wright, W.E., Lin, V., Lassar, A., Weintraub, H., and Buckingham, M., 1989, Expression of two myogenic regulator factors myogenin and MyoD1 during mouse embryogenesis, Nature (Lond.), 341: 303.

    Article  CAS  Google Scholar 

  • Satre, M.A., and D.M. Kochhar, 1989, Elevations in the endogenous levels of the putative morphogen retinoic acid in embryonic mouse limb buds associated with limb dysmorphogenesis, Dev. Biol., 133: 529.

    Article  PubMed  CAS  Google Scholar 

  • Saunders, J.W., Gasseling, M.T., and Saunders, L.C., 1962, Cellular death in morphogenesis in the avian wing, Dev. Biol., 5: 147.

    Article  PubMed  Google Scholar 

  • Saunders J.W., and Gasseling, M.T., 1968, Ectodermal-mesenchymal interactions in the origin of wing symmetry in: “Epithelial-mesenchymal Interactions,” R. Fleischmajer, and R.E. Billingham, eds., Williams and Wilkins, Baltimore, pp. 78–97.

    Google Scholar 

  • Schwartzberg, P.L., Goff, S.P., and Robertson, E.J., 1989, Germ-line transmission of a c-abl mutation produced by targeted gene disruption in ES cells, Science, 246: 799.

    Article  PubMed  CAS  Google Scholar 

  • Smith, J.C., 1989, Mesoderm induction and mesoderm-inducing factors in early amphibian development, Development, 105: 665.

    PubMed  CAS  Google Scholar 

  • Smith, J.C., 1989, Mesoderm induction and mesoderm-inducing factors in early amphibian development, Development, 105: 665.

    PubMed  CAS  Google Scholar 

  • Spemann,H., and Mangold, H., 1924, Ueber Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren, Wihelm Roux Arch., 100: 599.

    Google Scholar 

  • Stripe, N.S., and Goetnick, P.F. 1989, Gene regulation during cartilage differentiation: temporal and spatial expression of linkprotein and cartilage matrix protein in the developing limb, Development, 107: 23.

    Google Scholar 

  • Summerbell, D., 1983, The effects of local application of retinoic acid to the anterior margin of the developing chick limb, J. Embryol. Exp. Morphol., 78: 269.

    PubMed  CAS  Google Scholar 

  • Summerbell, L., Lewis, J.H., and Wolpert, L., 1973, Positional information in chick limb morphogenesis, Nature (Lond.), 224: 492.

    Article  Google Scholar 

  • Thaller, C., and Eichele, G., 1987, Identification and spatial distribution of retinoids in the developing chick limb bud, Nature (Lond.), 327: 625.

    Article  CAS  Google Scholar 

  • Thaller, C., and Eichele, G., 1988, Characterization of retinoid metabolism in the developing chick limb bud, Development, 103: 473.

    PubMed  CAS  Google Scholar 

  • Thompson, S., Clarke, A.R., Pow, A.M., Hooper, M.L., and Melton, D.W., 1989, Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells, Cell, 56: 313.

    Article  PubMed  CAS  Google Scholar 

  • Tickle, C., 1980, The polarizing region and limb development in: “Development in Mammals,” M.H. Johnson, ed., Elsevier/ North-Holland Biomedical Press, Amsterdam, (vol.4) pp. 101–136.

    Google Scholar 

  • Tickle, C., Lee, J., and Eichele, G., 1985, A quantitative analysis of the effect of all-trans-retinoic acid on the pattern of chick wing development, Dev. Biol., 109: 82.

    Article  PubMed  CAS  Google Scholar 

  • Tickle, C., Alberts, B.M., Wolpert, L., and Lee, J., 1982, Local application of retinoic acid to the limb bud mimics the action of the polarizing region, Nature (Lond.), 296: 564.

    Article  CAS  Google Scholar 

  • Tickle, C., Summerbell, D., and Wolpert, L., 1975, Positional signalling and specification of digits in chick limb morphogenesis, Nature (Lond.), 254: 199.

    Article  CAS  Google Scholar 

  • Tosney, K.W., Watanabe, M., Landmesser, L., and Rutishauser, U., 1986, The distribution of NCAM in the chick hindlimb during axon outgrowth and synaptogenesis, Dev.Biol., 114: 437.

    Article  PubMed  CAS  Google Scholar 

  • Weeks, D.L., and Melton, D.A., 1987, A maternal mRNA localized to the vegetal hemisphere in Xenopus eggs codes for a groth factor related to TGF-β, Cell, 51: 861.

    Article  PubMed  CAS  Google Scholar 

  • Wright, C.V.E., Cho, K.W.Y., Oliver, G., and DeRobertis, E.M., 1989, Vertebrate homeodomain proteins: families of region-specific transcription factors, Trends Biochem. Sci., 1: 52.

    Article  Google Scholar 

  • Yamamoto, K.R., 1985, Steroid receptor regulated transcription of specific genes and gene networks, Ann. Rev. Genet., 19: 209.

    Article  PubMed  CAS  Google Scholar 

  • Zelent, A., Krust, A., Petkovich, M., Kastner, P., and Chambon, P. 1989, Cloning of murine α and β retinoic acid receptors and a novel receptor g predominantly expressed in skin, Nature (Lond.), 339: 714.

    Article  CAS  Google Scholar 

  • Zeller, R., Jackson-Grusby, L., and Leder, P., 1989, The limb deformity gene is required for apical ectodermal ridge differentiation and anteroposterior limb pattern formation, Genes Dev., 3: 1481.

    Article  PubMed  CAS  Google Scholar 

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Eichele, G., Thaller, C. (1990). The Role of Retinoic Acid in Vertebrate Limb Morphogenesis. In: Marthy, HJ. (eds) Experimental Embryology in Aquatic Plants and Animals. NATO ASI Series, vol 195. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3830-1_21

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  • DOI: https://doi.org/10.1007/978-1-4615-3830-1_21

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