Retinoids in Nonmammalian Embryos

  • Malcolm Maden
Part of the METHODS IN MOLECULAR BIOLOGY™ book series (MIMB, volume 461)

1. Introduction

The family of retinoids comprise an enormous number of compounds related to vitamin A. Many of these compounds are naturally occurring substances generated during the biological functioning of retinoids: the conversion of dietary sources of retinoids (β-carotenes, retinyl esters) to those that can be taken up by the absorptive epithelium of the gut (retinol); the conversion of absorbed forms to stored forms in the liver (retinyl esters); the conversion of stored forms to active forms as mediators of vision (retinals), skin differentiation (retinoic acids), and general cell differentiation and proliferation (retinoic acids). However, more of these compounds are synthetic, for example, the retinobenzoic acids, and have been generated in the desire to find more potent and less teratogenic retinoids for pharmaceutical use. This chapter will be concerned only with a very few retinoids, ones that have been used in an embryological context.

The original definition of a...


Retinoic Acid Chick Embryo High Pressure Liquid Chromatography Elution Time Retinyl Palmitate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Sporn, M. B. and Roberts, A. B. (1985) What is a retinoid? Ciba Found. Symp. 113, 1–5.PubMedGoogle Scholar
  2. 2.
    Mangelsdorf, D. J., Umesono, K., and Evans, R. M. (1994) The retinoid reception, in The Retinoids. Biology, Chemistry and Medicine, 2nd ed. (Spore, M. B., Roberts, A. B., and Goodman D. S., eds.), Raven, New York, pp. 319–349.Google Scholar
  3. 3.
    Thaller, C. and Eichele, G. (1987) Identification and spatial distribution of retinoids in the developing chick limb bud. Nature 327, 625–628.CrossRefPubMedGoogle Scholar
  4. 4.
    Scott, W. J., Walter, R., Tzimas, G., Sass, J. O., Nau, H., and Collins, M. D. (1994) Endogenous status of retinoids and their cytosolic binding proteins in limb buds of chick vs mouse embryos. Dev. Biol. 165, 397–409.CrossRefPubMedGoogle Scholar
  5. 5.
    Horton, C. and Maden, M. (1995) Endogenous distribution of retinoids during normal development and teratogenesis in the mouse embryo. Dev. Dynam. 202, 312–323.Google Scholar
  6. 6.
    Sporn, M. B., Dunlop, V. M., Newton, D. L., and Henderson, N. R. (1976) Relationships between structure and activity of retinoids. Nature 263, 110–113.CrossRefPubMedGoogle Scholar
  7. 7.
    Lee, Q. P., Juchau, M. R., and Kraft, J. C. (1991) Microinjection of cultured rat embryos: Studies with retinol, 13-cis and all-trans-retinoic acid. Teratology 44, 313–323.CrossRefPubMedGoogle Scholar
  8. 8.
    Keeble, S. and Maden, M. (1989) The relationship among retinoid structure, affinity for retinoic acid-binding protein and ability to respecify pattern in the regenerating axolotl limb. Dev. Biol. 132, 26–34.CrossRefPubMedGoogle Scholar
  9. 9.
    Summerbell, D. and Harvey, F. (1983) Vitamin A and the control of pattern in developing limbs, in Limb Development and Regeneration, part A. (Fallon, J. and Caplan, A., eds.), Liss, New York, pp. 109–118.Google Scholar
  10. 10.
    Cadi, R., Pautou, M.-P., and Dhouailly, D. (1984) Structure-activity relationships in the morphogenesis of cutaneous appendages in the chick embryo. J. Investig. Dermatol. 83, 105–109.CrossRefPubMedGoogle Scholar
  11. 11.
    Durston, A. J., Timmermans, J. P. M., Hage, W. J., Hendriks, H. F. J., de Vries, N. J., Heideveld, M., and Nieuwkoop, P. D. (1989) Retinoic acid causes an antero-posterior transformation in the developing central nervous system. Nature 340, 140–144.CrossRefPubMedGoogle Scholar
  12. 12.
    Kraft, J. C., Schuh, T., Juchau, M., and Kimelman, D. (1994) The retinoid X receptor ligand, 9-cis-retinoic acid is a potential regulator of early Xenopus development. Proc. Natl. Acad. Sci USA 91, 3067–3071.CrossRefPubMedGoogle Scholar
  13. 13.
    Costaridis, P., Horton, C., Zeitlinger, Holder, N., and Maden, M. (1995) Endogenous retinoids in the zebrafish embryo and adult. Dev. Dynam. 205, 41–54.CrossRefGoogle Scholar
  14. 14.
    Thaller, C., Hofmann, C., and Eichele, G. (1993) 9-cis-retinoic acid, a potent inducer of digit pattern duplications in the chick wing bud. Development 118, 957– 965.PubMedGoogle Scholar
  15. 15.
    Chen, Y., Huang, L., Russo, A. F., and Solursh, M. (1992) Retinoic acid is enriched in Hensen's node and is developmentally regulated in the early chicken embryo. Proc. Natl. Acad. Sci. USA 89, 10,056–10,059.Google Scholar
  16. 16.
    Scadding, S. R. and Maden, M. (1994) Retinoic acid gradients in limb regeneration. Dev. Biol. 162, 608–617.CrossRefPubMedGoogle Scholar
  17. 17.
    Heyman, R. A., Mangelsdorf, D. J., Dyck, J. A., Stein, R., Eichele, G., Evans, R. M., and Thaller, C. (1992) 9-cis-retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 68, 397–406.CrossRefPubMedGoogle Scholar
  18. 18.
    Viviano, C. M., Horton, C., Maden, M., and Brockes, J. P. (1995). Synthesis and release of 9-cis-retinoic acid by the urodele wound epidermis. Development 121, 3753–3762.Google Scholar
  19. 19.
    Thaller, C. and Eichele, G. (1990) Isolation of 3,4-didehydroretinoic acid, a novel morphogenetic signal in the chick wing bud. Nature 345, 815–819.CrossRefPubMedGoogle Scholar
  20. 20.
    Pijnappel, W. W. M., Hendriks, H. F. J., Folkers, G. E., van den Brink, C. E., Dekker, E. J., Edelenbosch, C., van der Saag, P. T., and Durston, A. J. (1993) The retinoid ligand 4-oxo-retinoic acid is a highly active modulator of positional information. Nature 366, 340–344.CrossRefPubMedGoogle Scholar
  21. 21.
    Kraft, J. C., Bechter, R., Lee, Q. P., and Juchau, M. R. (1992) Microinjections of cultured rat conceptuses: Studies with 4-oxo-all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid and all-trans-retinoyl-β-glucuronide. Teratology 45, 259–270.CrossRefPubMedGoogle Scholar
  22. 22.
    Maden, M. (1983) The effect of vitamin A on the regenerating axolotl limb. J. Embryol. Exp. Morph. 77, 273–295.PubMedGoogle Scholar
  23. 23.
    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, 1913–1920.CrossRefPubMedGoogle Scholar
  24. 24.
    Tamura, K., Kagechika, H., Hashimoto, Y., Shudo, K., Oshugi, K., and Ide, H. (1990) Synthetic retinoids, retinobenzoic acids, Am80, AmS80 and Ch55 regulate morphogenesis in chick limb bud. Cell Differ. Dev. 32, 17–26.CrossRefPubMedGoogle Scholar
  25. 25.
    Maden, M., Summerbell, D., Maignan, J., Darmon, M., and Shroot, B. (1991) The respecification of limb pattern by new synthetic retinoids and their interaction with cellular retinoic acid-binding protein. Differentiation 47, 49–55.CrossRefPubMedGoogle Scholar
  26. 26.
    Maden, M., Keeble, S., and Cox, R. A. (1985) The characteristics of local application of retinoic acid to the regenerating axolotl limb. Roux's Arch. Dev. Biol. 194, 228–235.CrossRefGoogle Scholar
  27. 27.
    Tickle, C., Alberts, B., Wolpert, L., and Lee, J. (1982) Local application of retinoic acid to the limb bud mimics the action of the polarizing region. Nature 296, 564–565.CrossRefPubMedGoogle Scholar
  28. 28.
    Eichele, G., Tickle, C., and Alberts, B. M. (1984) Microcontrolled release of biologically active compounds in chick embryos: beads of 200 μm diameter for the local release of retinoids. Anal. Biochem. 142, 542–555.CrossRefPubMedGoogle Scholar
  29. 29.
    Summerbell, D. (1983) The effect of local application of retinoic acid to the anterior margin of the developing chick limb. J. Embryol. Exp. Morph. 78, 269–298.PubMedGoogle Scholar
  30. 30.
    Osmond, M. K., Butler, A. J., Voon, F. C. T., and Bellairs, R. (1991) The effects of retinoic acid on heart formation in the early chick embryo. Development 113, 1405–1417.PubMedGoogle Scholar
  31. 31.
    Sundin, O. and Eichele, G. (1992) An early marker of axial pattern in the chick embryo and its respecification by retinoic acid. Development 114, 841–852.PubMedGoogle Scholar
  32. 32.
    Drysdale, T. A. and Crawford, M. J. (1994) Effects of localized application of retin-oic acid on Xenopus laevis development. Dev. Biol. 162, 394–401.CrossRefPubMedGoogle Scholar
  33. 33.
    Thoms, S. D. and Stocum, D. L. (1984) Retinoic acid-induced pattern duplication in regenerating urodele limbs. Dev. Biol. 103, 319–328.CrossRefPubMedGoogle Scholar
  34. 34.
    Koussoulakos, S., Sharma, K. K., and Anton, H. J. (1988) Vitamin A induced bilateral asymmetries in Triturus forelimb regenerates. Biol. Structures Morphogenesis 1, 43–48.Google Scholar
  35. 35.
    Hill, J., Clarke, J. D. W., Vargesson, N., Jowett, T., and Holder, N. (1995) Exogenous retinoic acid causes specific alterations in the midbrain and hindbrain of the zebrafish embryo including positional respecification of the Mauthner neuron. Mech. Dev. 50, 3–16.CrossRefPubMedGoogle Scholar
  36. 36.
    Stainier, D. Y. R. and Fishman, M. C. (1992) Patterning the zebrafish heart tube: acquisition of anteroposterior polarity. Dev. Biol. 153, 91–101.CrossRefPubMedGoogle Scholar
  37. 37.
    Hyatt, G. A., Schmitt, E. A., Marsh-Armstrong, N. R., and Dowling, J. E. (1992) Retinoic acid induced duplication of the zebrafish retina. Proc. Natl. Acad. Sci. USA 89, 8293–8297.CrossRefPubMedGoogle Scholar
  38. 38.
    Geraudie, J., Brulfert, A., Monnot, M. J., and Ferretti, P. (1994) Teratogenic and morphogenetic effects of retinoic acid on the regenerating pectoral fin in zebrafish. J. Exp. Zool. 269, 12–22.CrossRefGoogle Scholar
  39. 39.
    Wagner, M., Han, B., and Jessell, T. M (1992) Regional differences in retinoid release from embryonic neural tissue detected by an in vitro reporter assay. Development 116, 55–66.PubMedGoogle Scholar
  40. 40.
    Packer, L. (1990) Retinoids. Part A Molecular and metabolic aspects. Meth. Enzy-mol. 189.Google Scholar
  41. 41.
    Cullum, M. E. and Zile, M. H. (1986) Quantitation of biological retinoid by high-pressure liquid chromatography: primary internal standardization using tritiated retinoids. Anal. Biochem. 153, 23–32.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Malcolm Maden
    • 1
  1. 1.MRC Centre for Developmental NeurobiologyKing's College LondonUK

Personalised recommendations