Retinoids and Embryos

  • Gillian Morriss-Kay
Part of the ESO Monographs book series (ESO MONOGRAPHS)


The highly controlled manner of growth and change in embryos appears at first sight to be a world apart from the apparent disorder of cancer. However, the enormous variety of biological processes within a single embryo may offer some useful parallels with the molecular and cellular basis of oncogenesis. The control of retinoid levels within embryos, and the effects of altered retinoid levels on development, are particularly relevant in this respect.


Retinoic Acid Hair Cell Retinoic Acid Receptor Noic Acid Retinoic Acid Synthesis 
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  1. 1.
    Bernfieid M, Banerjee SD, Koda J, Rapraeger AC: Remodeling of the basement membrane as a mechanism of morphogenetic tissue interaction. In: Trelstad RL, ed) The Role of Extracellular Matrix in Development. Alan R Liss, Inc, New York 1984 pp 545–572Google Scholar
  2. 2.
    Nakanishi Y, Morita T, Nogawa M: Cell proliferation is not required for the initiation of early cleft formation in mouse embryonic submandibular epithelium in vitro. Development 1987, (99):429–437PubMedGoogle Scholar
  3. 3.
    Morriss-Kay GM: Growth and development of pattern in the cranial neural epithelium of rat embryos during neurulation. J Embryol Exp Morph 1981, 65 suppl :(225)–241PubMedGoogle Scholar
  4. 4.
    Conlon RA and Rossant J: Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox-2 genes in vivo. Development 1992, (116) 357–368PubMedGoogle Scholar
  5. 5.
    Langman J, Guerrant RL, Freemen BG: Behavior of neuroepithelial cells during closure of the neural tube. J Comp Neurol, (127):399–412Google Scholar
  6. 6.
    Morriss-Kay G and Mahmood R: Morphogenesis-related changes in extracellular matrix induced by retinoic acid. In: Morriss-Kay GM, (ed) Retinoids in Normal Development and Teratogenesis. Oxford University Press, Oxford 1992 pp 165–180Google Scholar
  7. 7.
    Tuckett F, Morriss-Kay GM: A role for heparan sulphate proteoglycan in the rat embryo: effects of heparitinase treatment during early organogenesis. Anat Embryol 1989, (180):393–400PubMedCrossRefGoogle Scholar
  8. 8.
    Nüsslein-Volhard C and Wieschaus E: Mutations affecting segment number and polarity in Drosophila. Nature 1980, (287):795–801PubMedCrossRefGoogle Scholar
  9. 9.
    Ingham PW: Localised hedgehog activity controls spatially restricted transcription of wingless Drosophila embryo. Nature 1993, (366) :560–562PubMedCrossRefGoogle Scholar
  10. 10.
    Duboule D and Dolle P: The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. EMBO J 1989, (8):1497–1505PubMedGoogle Scholar
  11. 11.
    Graham A, Papalopulu N, Krumlauf R: The murine and Drosophila homeobox clusters have common features of organisation and expression. Cell 1989, (57):367–378PubMedCrossRefGoogle Scholar
  12. 12.
    Ingham P: Hedgehog points the way. Current Biology 1994, (4):347–350PubMedCrossRefGoogle Scholar
  13. 13.
    Mangelsdorf DJ, Umesono K, Evans RM: The retinoid receptors. In: Sporn MB, Roberts AB, Goodman DS, eds) The Retinoids. Raven Press Ltd, New York 1994 pp 319–349Google Scholar
  14. 14.
    Dolle P, Ruberte E, Kastner P, Petkovich M, Stoner CM, Gudas LJ, Chambon P: Differential expression of the genes encoding the retinoic acid receptors α, ß, γand CRABP in the developing limbs of the mouse. Nature 1989, (342):702–705PubMedCrossRefGoogle Scholar
  15. 15.
    Dolle P, Ruberte E, Leroy P, Morriss-Kay G, Chambon P: Retinoic acid receptors and cellular binding proteins I. A systematic study of their differential pattern of transcription during mouse organogenesis. Development 1990, (110):1133–1151PubMedGoogle Scholar
  16. 16.
    Ruberte E, Dolle P, Chambon P, Morriss-Kay G: Retinoic acid receptors and cellular binding proteins II. Their differential pattern of transcription during early morphogenesis in mouse embryos. Development 1991, (111):45–60PubMedGoogle Scholar
  17. 17.
    Ruberte E, Nakshatri H, Kastner P, Chambon P: Retinoic acid receptors and binding proteins in mouse limb development. In: GM Morriss-Kay, (ed) Retinoids in Normal Development and Teratogenesis. Oxford University Press, Oxford 1992 pp 99–111Google Scholar
  18. 18.
    Ruberte E, Friederich V, Morriss-Kay G, Chambon P: Differential distribution patterns of CRABP I and CRABP II transcripts during mouse embryogenesis. Development 1992, (115):973–987PubMedGoogle Scholar
  19. 19.
    Ruberte E, Friederich V, Chambon P, Morriss-Kay G: Retinoic acid receptors and cellular retinoid binding proteins III. Their differential transcript distribution during mouse nervous system development. Development 1993, (118):267–282PubMedGoogle Scholar
  20. 20.
    Mendelsohn C, Ruberte E, LeMeur M, Morriss-Kay G, Chambon P: Developmental analysis of the retinoic acid inducible RAR-62 promoter in transgenic animals. Development 1991, (113):723–734PubMedGoogle Scholar
  21. 21.
    Ong D and Chytil F: Cellular retinoic acid binding protein from rat testis. J Biol Chem 1978, (253):4551–4554PubMedGoogle Scholar
  22. 22.
    Bailey JS and Siu CH: Purification and partial characterization of a novel binding protein for retinoic acid from neonatal rat. J Biol Chem 1988, (263): 9326–9332PubMedGoogle Scholar
  23. 23.
    Giguere V, Lyn S, Yip P, Siu CH, Amin S: Molecular cloning of cDNA encoding a second cellular retinoic acid-binding protein. Proc Natl Acad Sci USA 1990, (87):6233–6237PubMedCrossRefGoogle Scholar
  24. 24.
    Napoli JL: Biosynthesis and metabolism of retinoic acid: roles of CRBP and CRABP in retinoic acid homeostasis. J Nutr 1993, (123):362–366PubMedGoogle Scholar
  25. 25.
    Lufkin T, Mark M, Hart CP et al: High postnatal lethality and testis degeneration in retinoic acid receptor a mutant mice. Proc Natl Acad Sci USA 1993, (90):7225–7229PubMedCrossRefGoogle Scholar
  26. 26.
    Lohnes D, Kastner p, Dierich A, Mark M, LeMeur M, Chambon P: Function of retinoic acid receptor y in the mouse. Cell 1993, (73):643–658PubMedCrossRefGoogle Scholar
  27. 27.
    Mendelsohn C, Mark M, Dolé P et al: Retinoic acid receptor ß2, RARß2) null mutant mice appear normal. Developmental Biology 1994, (in press)Google Scholar
  28. 28.
    Fell HB and Mellanby E: The effect of hyper-vitaminosis A on embryonic limb-bones cultivated in vitro. J Physiol 1952, (116):320–349PubMedGoogle Scholar
  29. 29.
    Shapiro SS and Mott DJ: Modulation of glycosaminoglycan biosynthesis by retinoids. Ann NY Acad Sci 1981, (359):306–321PubMedCrossRefGoogle Scholar
  30. 30.
    Kistler A: Hypervitaminosis A: side-effects of retinoids. Biochem Soc Trans 1986, (14):936–939PubMedGoogle Scholar
  31. 31.
    Creech Kraft J, Löfberg B, Chahoud I, Bochert G, Nau H: Teratogenicity and placental transfer of all-trans, 13-cis, 4-oxo-ali-trans, and 4-oxo-13-cis-retinoic acid after a low oral dose during organogenesis in mice. Toxicol Appl Pharmacol 1989, 100:162–176PubMedCrossRefGoogle Scholar
  32. 32.
    Satre MA and Kochhar DM: Elevations in the endogenous levels of the putative morphogen retinoic acid in embryonic mouse limb buds associated with limb dysmorphogenesis. Devel Biol 1989, (133):529–536CrossRefGoogle Scholar
  33. 33.
    Ward SJ and Morriss-Kay GM: Distribution of all- trans-, 13-eis- and 9-cis-retinoic acid to whole rat embryos and maternal serum following oral administration of a teratogenic dose of all-frans-retinoic acid. Pharmacol Toxicol 1994, in press)Google Scholar
  34. 34.
    Wood H, Pall G, Morriss-Kay G: Exposure to retinoic acid before or after the onset of somitogenesis reveals separate effects on rhombomeric segmentation and 3’ HoxB gene expression domains. Development 1994, (120):2279–2285PubMedGoogle Scholar
  35. 35.
    Ward S: The roles of retinoic acid in normal and abnormal mammalian limb development. Ph.D. thesis, University of Oxford, 1994Google Scholar
  36. 36.
    Mahmood R, Flanders KC, Morriss-Kay GM: Interactions between retinoids and TGF-ßs in mouse morphogenesis. Development 1992, (115):67–74PubMedGoogle Scholar
  37. 37.
    Morriss-Kay GM: Retinoic acid and craniofacial development: molecules and morphogenesis. Bio-Essays 1993, (15):9–15Google Scholar
  38. 38.
    Lammer EJ, Chen DT, Hoar RM et al: Retinoic acid embryopathy. New Engl J Med 1985, (313):837–841PubMedCrossRefGoogle Scholar
  39. 39.
    Kochhar DM: Limb development in mouse embryos. I. Analysis of teratogenic effects of retinoic acid. Teratology 1973, (11):289–298CrossRefGoogle Scholar
  40. 40.
    Kelley MW, Xu XM, Wagner MA, Warchol ME, Corwin JT: The developing organ of Corti contains retinoic acid and forms supernumerary hair cells in response to exogenous retinoic acid in culture. Development 1993, (119):1041–1053PubMedGoogle Scholar
  41. 41.
    Shenai JP, Kennedy KA, Chytil F, Stahlman MT: Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia. J Pediatr 1987, (111):269–277PubMedCrossRefGoogle Scholar
  42. 42.
    Wessels NK: Mammalian lung development: interactions in formation and morphogenesis of tracheal buds. J Exp Zool 1970, (175):455–466CrossRefGoogle Scholar
  43. 43.
    Cuschieri A and Bannister LH: The development of the olfactory mucosa in the mouse: light microscopy. J Anat 1975, (119):277–286PubMedGoogle Scholar
  44. 44.
    Pall GS: The effects of excess retinoic acid on the expression of retinoid signalling pathway genes and morphogenesis in mouse embryos. M.Sc. thesis, University of Oxford, 1994Google Scholar
  45. 45.
    Cornic M, Delva L, Guidez F, Balitrand N, Degos L, Chomienne C: Induction of retinoic acid-binding protein in normal and malignant myeloid cells by retinoic acid in acute promyelocytic leukemia patients. Cancer Res 1992, (52):3329–3334PubMedGoogle Scholar
  46. 46.
    Yang-Yen H-F, Zhang X-K, Graupner G, Tzukerman M, Sakamoto B, Karin M, Pfahl M: Antagonism between retinoic acid receptors and AP-1: Implications for tumor promotion and inflammation. New Biologist 1991, (3):1206–1220PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Gillian Morriss-Kay
    • 1
  1. 1.Department of Human AnatomyUniversity of OxfordOxfordUK

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