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)
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Arias, A.M., 1989, A cellular basis for pattern formation in the insect epidermis, Trends Genet., 5: 262.
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.
Beato, M., 1989, Gene regulation by steroid hormone, Cell, 56: 335.
Benbrook, D., Lernhardt, E., and Pfahl, M., 1988, A new retinoic acid receptor identified from rat hepatocellular carcinoma, Nature (Lond.), 333: 669.
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.
Brockes, J.P., 1989, Retinoids, homeobox genes, and limb morphogenesis, Neuron, 2: 1285.
Bryant, S.V., French, V., Bryant, P.J., 1981, Distal regeneration and symmetry, Science, 212: 993.
Bryant, S.,V., and Muneoka, K., 1986, Views of limb development and regeneration, Trends Genet., 2: 153.
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.
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
Cooke, J. and Summerbell, D., 1980, Cell cycle and experimental pattern duplication in the chick wing during embryonic development, Nature (Lond.), 287: 697.
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,
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.
Douer, D, and Koeffler, H.P., 1982, Inhibition of clonal growth of human myeloid leukemia cells, J. Clin. Invest., 69: 277.
Dowling, J.E., and Wald, G., 1960, The biological function of vitamin A acid, Proc. Natl. Acad. Sci., 46: 587.
Eichele, G., 1989, Retinoids and vertebrate limb pattern formation, Trends Genet., 5: 246.
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.
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.
Evans, R.M., 1988, The steroid and thyroid hormone receptor super-family, Science, 240: 889.
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.
Gehring, W.J., 1987, Homeo boxes in the study of development, Science, 236: 1245.
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.
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.
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.
Green, S., and Chambon, P., (1988), Nuclar receptors enhance our understanding of transcriptional regulation, Trends Genet., 4: 309.
Greenwald, I., 1989, Cell-cell interactions that specify cell fates in C. elegans in development, Trends Genet., 5: 237.
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.
Hamburger, V., and Hamilton, H., 1951, A series of normal stages in the development of the chick embryo, J. Morph., 88: 49.
Hinchliffe, J.R., and Johnson, D.R., 1980, “The Development of the Vertebrate Limb,” Clarendon Press, Oxford.
Holland P. W. H., and Hogan, B. L. M., 1988, Expression of homeobox genes during mouse development: a review, Genes Dev., 2: 773.
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.
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.
Jaenisch, R., 1988, Transgenic animals, Science, 240: 1468.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Newman, S.A., 1988, Lineage and pattern in the developing vertebrate limb, Trends Genet., 4: 329.
O’Rahilly, R., and Gardener, E., 1975, The timing and sequence of the limbs in the human embryo, Anat. Embryol., 148: 1.
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.
Peifer, M., Krach, F., and Bender, W., 1988, The bithorax complex: control and segmental identity, Genes Dev., 1: 891.
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.
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.
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.
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.
Rubin, G.M., 1989, Development of Drosophila retina: inductive events studied at single cell resolution, Cell, 57: 519.
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.
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.
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.
Saunders, J.W., Gasseling, M.T., and Saunders, L.C., 1962, Cellular death in morphogenesis in the avian wing, Dev. Biol., 5: 147.
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.
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.
Smith, J.C., 1989, Mesoderm induction and mesoderm-inducing factors in early amphibian development, Development, 105: 665.
Smith, J.C., 1989, Mesoderm induction and mesoderm-inducing factors in early amphibian development, Development, 105: 665.
Spemann,H., and Mangold, H., 1924, Ueber Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren, Wihelm Roux Arch., 100: 599.
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.
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.
Summerbell, L., Lewis, J.H., and Wolpert, L., 1973, Positional information in chick limb morphogenesis, Nature (Lond.), 224: 492.
Thaller, C., and Eichele, G., 1987, Identification and spatial distribution of retinoids in the developing chick limb bud, Nature (Lond.), 327: 625.
Thaller, C., and Eichele, G., 1988, Characterization of retinoid metabolism in the developing chick limb bud, Development, 103: 473.
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.
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.
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.
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.
Tickle, C., Summerbell, D., and Wolpert, L., 1975, Positional signalling and specification of digits in chick limb morphogenesis, Nature (Lond.), 254: 199.
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.
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.
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.
Yamamoto, K.R., 1985, Steroid receptor regulated transcription of specific genes and gene networks, Ann. Rev. Genet., 19: 209.
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.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Springer Science+Business Media New York
About this chapter
Cite this chapter
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
Download citation
DOI: https://doi.org/10.1007/978-1-4615-3830-1_21
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6709-3
Online ISBN: 978-1-4615-3830-1
eBook Packages: Springer Book Archive