Abstract
Vitamin A and metabolites (retinoids) control numerous processes which are critical for reproduction and development such as differentiation, proliferation, apoptosis and morphogenesis (De Luca et al. 1995). Evidence has accumulated since the discovery of the retinoid receptors a decade ago (Petkovic et al. 1987; Giguere et al. 1987) that these nuclear receptors may be involved in many of these processes. Retinoid receptors are ligand-activated transcription factors which control the expression of a number of target genes involved in development such as growth factors, growth factor receptors, cell adhesion molecules, intercellular matrix molecules, other transcription factors such as hox genes, some hormones and cytokines, as well as other receptors of the hormone receptor superfamily; furthermore, retinoid pathways themselves are influenced via the control of expression of retinoid binding proteins, metabolizing enzymes and autoregulation of retinoid receptors (Kastner et al. 1995; Chambon 1996; Morris-Kay and Sokolova 1996; Van Der Saag 1996; Nagpal and Chandrarathna 1996; Smith et al. 1998).
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References
Achkar CC, Derguini F, Blumberg B, Langstom A, Levin AA, Speck J, Evans RM, Bolado Jr J, Nakanishi K, Buck J, Gudas LJ (1996) 4-oxoretinol, a new natural ligand and transactivator of the retinoic acid receptors. Proc Natl Acad Sci USA 93:4879–4884
Allenby G, Bocquel MT, Saunders M, Kazmer S, Speck J, Rosenberger M, Lovey A, Kastner P, Grippo JF, Chambon P, Levin AA (1993) Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci USA 90:30–34
Apfel C, Bauer F, Crettaz M, Forni L, Kauber M, Kaufmann F, LeMotte P, Pirson W, Klaus M (1992) A retinoic acid receptor α antagonist selecitively counteracts retinoic acid effects. Proc Natl Acad Sci USA 89:7129–7133
Arafa HMM, Hamada FMA, Elmazar MMA, Nau H (1996) Fully automated determination of selective retinoic acid receptor ligands in mouse plasma and tissue by reversed-phase liquid chromatography coupled on-line with solid-phase extraction. J Chromatogr A 729:125–136
Arnhold T, Tzimas G, Wittfoht W, Plonait S, Nau H (1996) Identification of 9-cis-retinoic acid, 9,13-di-cis-retinoic acid, and 14-hydroxy-4,14-retro-retinol in human plasma after liver consumption. Life Sci 59: PL 169–177
Bavik C, Ward SJ, Chambon P (1996) Developmental abnormalities in cultured mouse embryos deprived of retinoic acid by inhibition of yolk-sac retinol binding protein synthesis. Proc Natl Acad Sci USA 93:3110–3114
Bernard BA, Bernardon JM, Delescluse C, Martin B, Lenoir MC, Maignan J, Charpentier B, Pilgrim WR, Reichert U, Shroot B (1992) Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor ß. Biochem Biophys Res Commun 186: 977–
Biesalski HK (1997) Bioavailability of vitamin A. Eur J Clin Nutr 51:S71-S75
Blumberg B, Bolado Jr J, Derguini F, Craig AG, Moreno TA, Chakravarti D, Heyman RA, Buck J, Evans RM (1996) Novel retinoic acid receptor ligands in Xenopus embryos. Proc Natl Acad Sci USA 93:4873–4878
Brinkmann E, Dehne L, Bijosono Oei H, Tiebach R, Baltes W (1995) Separation of geometrical retinol isomers in food samples by using narrow-bore high performance liquid chromatography. J Chromagr A 693:271–279
Buchan P, Eckhoff C, Caron D, Nau H, Shroot B, Schaefer H (1994) Repeated topical administration of all-trans-retinoic acid and plasma levels of retinoic acids in man. J Am Acad Dermatol 30:428–434
Chambon P (1996) A decade of molecular biology of retinoic acid receptors. FASEB J 10:940–954
Chen JY, Clifford J, Zusi C, Starrett J, Tortolani D, Ostrowski J, Reczek PR, Chambon P, Gronemeyer H (1996) Two distinct actions of retinoid-receptor ligands. Nature 382:819–822
Chen WH, Morriss-Kay GM, Copp A (1995) Genesis and prevention of spinal neural tube in the curly tail mutant mouse: involvement of retinoic acid and its nuclear receptors RAR-ß and RAR-γ Development 121:681–691
Chen Y, Huang L, Russo AF, 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 89:10056–10059
Coberly S, Lammer E, Alashari M (1996) Retinoic acid embryopathy: case report and review of literature. Pediat Path Labor Med 16:823–836
Creech Kraft J, Schuh T, Juchau MR, 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
Crettaz M, Baron A, Siegenthaler G, Hunziker W (1990) Ligand specificities of recombinant retinoic acid receptors RAR-α and RAR-ß. Biochem J 272:391–397
Darmon M, Rocher M, Cavey MT, Martin B, Rabilloud T, Delescluse C, Baily J, Eustache J, Jamoulle JC, Nedoncelle P, Shroot B (1989) Affinity of retinoids for nuclear receptors correlates with biological activity by absence of correlation with CRABP binding. In: U. Reichert, B. Shroot (eds) Pharmacology of retinoids in the skin, vol3. Karger, Basel, pp 56–64
Dekker EJ, Vaessen M-J, van der Berg C, Timmermans A, Godsave S, Holling T, Nieuwkoop P, Geurts van Kessel A, Durston A (1994) Overexpression of a cellular retinoic acid binding protein (xCRABP) causes anteroposterior defects in developing Xenopus embryos. Development 120:973–985
De Luca LM, Darwiche N, Jones CS Scita G (1995) Retinoids in differentiation and neoplasia. Sci Amer Sci Med July/August:28–37
Dickman ED, Thaller C, Smith SM (1997) Temporally-regulated retinoic acid depletion produces specific crest, ocular and nervous system defects. Development 124:3111–3121
Dollé P, Ruberte E, Kastner P, Petkovich M, Stoner CM, Gudas LJ, Chambon P (1989) Differential expression of genes encoding α, ß and γ retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature 342:702–705
Dolle P, Ruberte E, Leory P, Morriss-Kay G, Chambon P (1990) Retinoic acid receptors and cellular retinoid binding proteins I. A systematic study of their differential pattern of transcription during mouse organogenesis. Development 110:1133–1151
Duester G (1998) Alcohol dehydrogenase as a critical mediator of retinoic acid synthesis from vitamin A in mouse embryo. J Nutr 128:459S–462s
Durand B, Saunders M, Gaudon C, Roy B, Losson R, Chambon P (1994) Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: Presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element of AF-2 activity. EMBO J 13:5370–5382
Durand B, Saunders M, Leroy P, Leid M, Chambon P (1992) All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs. Cell 71:73–85
Durston AJ, Timmermans JPM, Hage WJ, Hendriks HFJ, de Vires NJ, Heideveld M, Nieuwkoop PD (1989) Retinoic acid causes an anteroposterior transformation in the developing central nervous system. Nature 340:140–144
Eckhardt K, Schmitt G (1994) A retinoic acid receptor α antagonist counteracts retinoid teratogenicity in vitro and reduced incidence and/or severity of malformations in vivo. Toxicol Lett 70:299–308
Eckhoff C, Collins MD, Nau H (1991) Human plasma all-trans-, 13-cis-, and 13-cis-4-oxoretinoic acid profiles during subchronic vitamin A supplementation: Comparison to retinol and retinyl ester plasma levels. J Nutr 121:1016–1025
Eckhoff C, Nau H (1990) Identification and quantitation of all-trans, 13-cis-, and 13-cis-4-oxoretinoic acid in human plasma. J Lipid Res 31:1445–1454
Elmazar MMA, Reichert U, Shroot B, Nau H (1996) Pattern of retinoid-induced teratogenic effects: Possible relationship with relative selectivity for nuclear retinoid receptors RARα, RARß and RARγ. Teratology 53:158–167
Elmazar MMA, Rühl R, Reichert U, Shroot B, Nau H (1997) RARα-mediated teratogenicity in mice is potentiated by an RXR agonist and reduced by an RAR antagonist: Dissection of retinoid receptor-induced pathways. Toxicol Appl Pharmacol 146:21–28
Fiorella PD, Olson JR, Napoli JL (1995) 2,3,7,8-tetrachlorodibenz-p-dioxin induces diverse retinoic acid metabolites in multiple tissues of the Sprague-Dawley rat. Toxicol Appl Pharmacol 134:222–228
Ghyselinck NB, Dupé V, Dierich A, Messaddeq, Gamier JM, Rochette-Egly C, Chambon P, Mark M (1997) Role of retinoic acid receptor beta (RARß) during mouse development. Int J Dev Biol 41:425–447
Giguère V, Ong ES, Segui P, Evans RM (1987) Identification of a receptor for the morphogen retinoid acid. Nature 330:624–629
Gorry P, Lufkin T, Dierich A, Rochette-Egly C, Decimo D, Dolle P, Mark M, Durand B, Chambon P (1994) The cellular retinoic acid binding protein I is dispensable. Proc Natl Acad Sci USA 91:9032–9036
Gudas LJ (1994) Retinoids and vertebrate development. J Biol Chem 269:15399–15402
Gustafson A-L, Dencker L, Eriksson U (1993) Non-overlapping expression of CRBP I and CRABP I during pattern formation of limbs and craniofacial structures in the early mouse embryo. Development 117:451–460
Gyselinck et al. (1997)
Haselbeck RJ, Ang HL, Deltour L, Duester G (1997) Retinoic acid and alcohol/retinol dehydrogenase in the mouse adrenal gland: a potential endocrine source of retinoic acid during development. Endocrinology 138:3035–3041
Hashimoto Y, Shudo K (1991) Retinoids and their nuclear receptors. Cell Biol Rev 25:209–230
Helms JA, Chang HK, Eichele G, Thaller C (1996) Retinoic acid signaling is required during early chick limb development. Development 122:1385–1394
Helms JA, Kim CH, Hu D, Minkoff R, Thaller C, Eichele G (1997) Sonic hedgehog participates in craniofacial morphogenesis and is down-regulated by teratogenic doses of retinoic acid. Dev Biol 187:25–35
Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C (1992) 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 68:397–406
Imai S, Okuno M, Moriwaki H, Muto Y, Murakami K, Shudo K, Suzuki Y, Kojima S (1997) 9,13-di-cis Retinoic acid induces the production of PA and activation of latent TGF-ß via RARa in a human liver stellate cell line, LI90. FEBS Lett 411:102–106
Iulianella A, Lohnes D (1997) Contribution of retinoic acid receptor gamma to retinoid-induced craniofacial and axial defects. Dev Dyn 209:92–104
Jiang H, Penner JD, Beard RL, Chandraratna RAS, Kochhar DM (1995a) Diminished teratogenicity of retinoid X receptor-selective synthetic retinoids. Biochem Pharmacol 50 669–676
Jiang H, Soprano DR, Li SW, Soprano KJ, Penner JD, Gyda III M, Kochhar DM (1995b) Modulation of limb bud chondrogenesis by retinoic acid and retinoic acid receptors. Int J Dev Biol 39:617–627
Kastner P, Grondona JM, Mark M, Gansmuller A, LeMeur M, Decimo D, Vonesch JL, Dollé P, Chambon P (1994) Genetic analysis of RXRα developmental function: Convergence of RXR and RAR signaling pathways in heart and eye morphogenesis. Cell 78:987–1003
Kastner P, Mark M, Chambon P (1995) Nonsteroid nuclear receptors: What are genetic studies telling us about their role in real life? Cell 83:859–869
Kastner P, Mark M, Ghyselnick N, Krezel W, Dupé V, Grondona JM, Chambon P (1997) Genetic evidence that the retinoid signal is transduced by heterodimeric RXR/RAR functional units during mouse development. Development 124:313–326
Kastner P, Mark M, Leid M, Gansmuller A, Chin W, Grondona JM, Décimo D, Krezel W, Dierich A, Chambon P (1996) Abnormal spematogenesis in RXRß mutant mice. Gen Dev 10:80–92
Kochhar DM, Jiang H, Penner JD, Beard RL, Chandraratna RAS (1996) Differential teratogenic response of mouse embryos to receptor selective analogs of retinoic acid. Chem Biol Interact 100:1–12
Krezel W, Dup é V, Mark M, Dierich A, Kastner P, Chambon P (1996) RXRγnull mice are apparently normal and compound RXRα +/−/RXRß−/−/RXRγ/−/− mutant mice are viable. Proc Natl Acad Sci USA 93:9010–9014
Krezel W, Ghyselinck N, Samad TA, Dupé V, Kastner P, Borrelli E, Chambon P (1998) Impaired locomotion and dopamine signaling in retinoid receptor mutant mice. Science 279:863–867
Kurlandsky SB, Gamble MV, Ramakrishnan R, Blaner WS (1995) Plasma delivery of retinoic acid to tissues in the rat. J Biol Chem 270:17850–17857
Lammer EJ, Chen DT, Hoar RM, Agnish ND, Benke PJ, Braun JT, Curry CJ, Fernhoff PM, Grix Jr AW, Lott IT, Richard JM, Sun SC (1985) Retinoic acid embryopathy. New Engl J Med 313:837–841
Lee JS, Newman RA, Lippman SA, Fossella FV, Calayag M, Raber MN, Krakoff IH, Hong WK Phase I evaluation of all-trans retinoic acid with and without ketoconazole in adults with solid tumours. J Clin Oncol 13:1501–1508
Lehmann JM, Dawson MI, Hobbs PD, Husmann M, Pfahl M (1991) Identification of retinoids with nuclear receptor subtype-selective activities. Cancer Res 51: 4804–4809 Lemotte PK, Keidel S, Apfel CM (1996) Phytanic acid is a retinoid X receptor ligand. Eur J Biochem 236:328-333
Levin AA, Sturzenbecker LJ, Kazmer S, Bosakowski T, Huselton C, Allenby G, Speck J, Kratzeisen C, Rosenberger M, Lovey A, Grippo JF (1992) 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRa. Nature 355:359–361
Li E, Norris AW (1996) Structure/function of cytoplasmic vitamin A-binding proteins. Annu Rev Nutr 16:205–234
Lohnes D, Kastner P, Dierich A, Mark M, LeMeur M, Chambon P (1993) Function of retinoic acid receptor γ in the mouse. Cell 73:643–658
Lohnes D, Mark M, Mendelsohn C, Dollé P, Decimo D, LeMeur M, Dierich A, Gorry P, Chambon P (1995) Developmental roles of retinoic acid receptors. J Steroid Biochem Mol Biol 53:475–486
Lohnes D, Mark M, Mendelsohn C, Dollé P, Dierich A, Gorry P, Gansmuller A, Chambon P (1994) Function of the retinoic acid receptors (RARs) during development (I) Craniofacial and skeletal abnormalities in RAR double mutants. Development 120:2733–3748
Lotan R, Dawson MI, Zou CC, Jong L, Lotan D, Zou CP (1995) Enhanced efficacy of combinations of retinoic acid-and retinoid X receptor-selective retinoids and α-interferon in inhibition of cervical carcinoma cell proliferation. Cancer Res 55:232–236
Lufkin T, Lohnes D, Mark M, Dierich A, Gorry P, Gaub MP, LeMeur M, Chambon P (1993) High postnatal lethality and testis degeneration in retinoic acid receptor α mutant mice. Proc Natl Acad Sci USA 90:7225–7229
Luo J, Pasceri P, Conlon RA, Rossant J, Giguère (1995) Mice lacking all isoforms of retinoic acid receptor ß develop normally and are susceptible to the teratogenic effects of retinoic acid. Mech Dev 53:61–71
Maden M (1994) Vitamin A in embryonic development. Nutr Rev 52: S3–S12
Maden M, Gale E, Zile MH (1998) The role of vitamin A in the development of the central nervous system. J Nutr 128:471S–475s
Maden M, Summerbell D, Maignan J, Darmon M, 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
Mangelsdorf DJ, Umesono K, Evans RM (1994) The retinoid receptors. In: MB Sporn, AB Roberts, DS Goodman (eds) The retinoids: biology, chemistry, and medicine. Raven, New York, pp 319–349
Martin B, Bernadon J-M, Cavey M-T, Bernard B, Carlavan I, Charpentier B, Pilgrim WR, Shroot B, Reichert U (1992) Selective synthetic ligands for human nuclear retinoic acid receptors. Skin Pharmacol 5:57–65
McCaffery, Dräger U (1994) Hot spots of retinoic acid synthesis in the developing spinal cord. Proc Natl Acad Sci USA 91:7194–7197
Mendelsohn C, Lohnes D, Décimo D, Lufkin T, LeMeur M, Chambon P, Mark M (1994b) Function of the retinoic acid receptors (RARs) during development (II) Multiple abnormalities at various stages of organogenesis in RAR double mutants. Development 120:2749–2771
Minucci S, Leid M, Toyama R, Saint-Jeannet JP, Peterson VJ, Horn V, Ishmael JE, Bhattacharyya N, Dey A, Dawid IB, Ozato K (1997) Retinoid X Receptor (RXR) within the RXR-retinoic acid receptor heterodimer binds its ligand and enhances retinoid-dependent gene expression. Mol Cell Biol 17:644–655
Minucci S, Saint-Jeannet JP, Toyama R, Scita G, DeLuca LM, Taira M, Levin AA, Ozato K, Dawid IB (1996) Retinoid X receptor-selective ligands produce malformations in Xenopus embryos. Dev Biol 93:1803–1807
Morriss-Kay GM, Sokolova N (1996) Embryonic development and pattern formation. FASEB J 10:961–968
Morse DC, Brouwer A (1995) Fetal, neonatal, and long-term alterations in hepatic retinoid levels following maternal polychlorinated biphenyl exposure in rats. Toxicol Appl Pharmacol 131:175–182
Motoyama J, Eto K (1994) Antisense retinoic acid receptor ß-1 oligonucleotide enhances chondrogenesis of mouse limb mesenchymal cells in vitro. FEBS Lett 338:319–322
Mukherjee R, Davies PJA, Crombie DL, Bischoff ED, Cesario RM, Jow L, Hamnn LG, Boehm MF, Mondon CE, Nadzan AM, Paterniti Jr JR, Heyman RA (1997) Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonist. Nature 386:407–410
Napal S, Chandraratna RAS (1996) Retinoids as anti-cancer agents. Curr Pharm Design 2:295–316
Nau (1990) Correlation of transplacental and maternal pharmacokinetics of retinoids during organogenesis with teratogenicity. Methods Enzymol 190:437–448
Nau H (1993) Embryotoxicity and teratogenicity of topical retinoic acid. Skin Pharmacol 6 [Suppl l]:35–44
Nau H (1994) Toxicokinetics and structure — activity relationships in retinoid teratogenesis. Ann Oncol 5 [Suppl 9]:S39–S43
Nau H, Chahoud I, Dencker L, Lammer E, Scott WJ (1994) Teratogenicity of vitamin A and retinoids. In: R Blomhoff (ed) Vitamin A in health and disease. Dekker, New York, pp 615–664
Nau H, Tzimas G, Mondry M, Plum C, Spohr H-L (1995) Antiepileptic drugs alter endogenous retinoid concentrations: a possible mechanism of teratogenesis of anticonvulsant therapy. Life Sci 57:53–60
Newcomer ME, Ong DE (1990) Purification and crystallization of retinoic acid-binding protein from rat epididymis. Identify with the major androgen-dependent epididymal proteins. J Biol Chem 265:12876–12879
Noji S, Nohno T, Koyama E, Muto K, Ohyama K, Aoki Y, Tamura K, Ohsugi K, Ide H, Taniguchi S, Saito T (1991) Retinoic acid induces polarizing activity but is unlikely to be a morphogen in the chick limb bud. Nature 350:83–86
Olson JA (1987) Recommended dietary intakes (RDI) of vitamin A in humans. Am J Clin Nutr 45:704–716
Petkovich M, Brand NJ, Krust A, Chambon P (1987) A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 330:444–450
Pignatello MA, Kaufmann FC, Levin AA (1997) Multiple factors contribute to the toxicity of the aromatic retinoid, TTNPB (7413-7410): binding affinities and disposition. Toxicol Appl Pharmacol 142:319-327
Repa JJ, Hanson KK, Clagett-Dame M (1993) All-trans-retinol is a ligand for the retinoic acid receptors. Proc Natl Acad Sci USA 90:7293–7297
Rosa FW, Wilk AL, Kelsey (1986) Teratogen update: vitamin A congeners. Teratology 33:355–364
Roy B, Taneja R, Chambon P (1995) Synergistic activation of retinoic acid (RA)-responsive genes and induction of embryonal carcinoma cell differentiation by an RA receptor α(RARα)-, RAR-ß-, or RAR-γ-selective ligand in combination with a retinoid X-receptor-specific ligand. Mol Cell Biol 15:6481–6487
Ruberte E, Dollé P, Chambon P, Morriss-Kay G (1991) Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryos. Development 111:45–60
Ruberte E, Dolé P, Krust A, Zelent A, Morriss-Kay G, Chambon P (1990) Specific spatial and temporal distribution of retinoic acid receptor gamma transcripts during mouse embryogenesis. Development 108:213–222
Ruberte E, Friederrich V, Chambon P, Morriss-Kay G (1993) Retinoic acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse nervous system development. Development 118:267–282
Sani BP, Venepally PR, Levin AA (1997) Didehydroretinoic acid: retinoid receptor mediated transcriptional activation and binding properties. Biochem Pharmacol 53:1049–1053
Sapin V, Ward SJ, Bronner S, Chambon P (1997) Differential expression of transcripts encoding retinoid binding proteins and retinoic acid receptors during placentation of the mouse. Dev Dyn 208:199–210
Satre MA, Kochhar DM (1989) Elevations of the endogenous levels of the putative morphogen retinoic acid in embryonic mouse limb-buds associated with limb dysmorphogenesis. Dev Biol 133:529–536
Schadendorf D, Kern MA, Artuc M, Pahl H, Rosenbach T, Fichtner I, Nürnberg W, Suting S, v. Stebut E, Worm M, Makki A, Jurgovsky K, Kolde G, Henz BM (1996) Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo. J Cell Biol 135:1889–1898
Scott WJ, Walter R, Tzimas G, Sass JO, Nau H, Collins MD (1994) Endogenous status of retinoids and their cytosolic binding proteins in limb buds of chick vs. mouse embryos. Dev Biol 165:397–409
Smith SM, Dickman ED, Power SC, Lancman J (1998) Retinoids and their receptors in vertebrate embryogenesis. J Nutr 128:467S–470S
Soprano DR, Gyda III M, Jiang H, Harnish DC, Ugen K, Satre M, Chen L, Soprano KJ, Kochhar DM (1994) A sustained elevation in retinoic acid receptor-β mRNA and protein occurs during retinoic acid-induced fetal dysmorphogenesis. Mech Dev 45:243–253
Soprano DR, Wyatt ML, Dixon JL, Soprano KJ, Goodman DWS (1988) Retinol binding protein synthesis and secretion by the rat visceral yolk sac: Effect of retinol status. J Biol Chem 263:2934–2938
Standeven AM, Johnson AT, Escobar M, Chandraratna RAS (1996) Specific antagonist of retinoid toxicity in mice. Toxicol Appl Pharmacol 138:169–175
Sucov HM, Dyson E, Gumeringer CL, Price J, Chien KR, Evans RM (1994) RXR α mutant mice establish a genetic basis for vitamin A signaling in heart morphogenesis. Genes Dev 8:1007–1018
Sucov HM, Izpisua-Belmonte JC, Ganan Y, Evans RM (1995) Mouse embryos lacking RXRαare resistant to retinoic acid-induced limb defects. Development 121:3997–4003
Takeyama K, Kojima R, Ohashi T, Sato T, Mano H, Masushige S, Kato S (1996) Retinoic acid differentially up-regulates the gene expression of retinoic acid receptors α and ß isoforms in embryo and adult rats. Biochem Biophys Res Commun 222:395–400
Tamura K, Hashimoto Y, Shudo K, Ide H (1993) Distribution of retinoids applied exogenously to chick limb buds: An autoradiographic analysis. Dev Growth Diff 35:593–599
Thaller C, Eichele G (1987) Identification and spatial distribution of retinoids in the developing chick limb bud. Nature 327:625–628
Thaller C, Hofmann C, Eichele G (1993) 9-cis-retinoic acid, a potent inducer of digit pattern duplications in the chick wing bud. Development 118:957–965
Tzimas G, Collins MD, Börgin H, Hummler H, Nau H (1996) Embryotoxic doses of Vitamin A to rabbits result in low plasma but high embryonic concentrations of all-trans-retinoic acid: Risk of Vitamin A exposure in humans. J Nutr 126:2159–2171
Tzimas G, Thiel R, Chahoud I, Nau H (1997) The area under the concentration-time curve of all-trans-retinoic acid is the most suitable pharmacokinetic correlate to the embryotoxicity of this retinoid in the rat. Toxicol Appl Pharmacol 143:436–444
van der Saag PT (1996) Nuclear retinoid receptors: Mediators of retinoid effects. Eur J Clin Nutr 50:S24–S28
Wagner M, Thaller C, Jessell T, Eichele G (1990) Polarizing activity and retinoid synthesis in the floor plate of the neural tube. Nature 345:819–822
Ward SJ, Chambon P, Ong DE, Bavik C (1997) A retinol-binding protein receptor mediated mechanism for uptake of vitamin A to postimplantation rat embryos. Biol Reprod 57:751–755
Watkins PA, Howard AE, Gould SJ, Avignan J, Mohalik SJ (1996) Phytanic acid activation in rat liver peroxisomes is catalyzed by long-chain acyl-CoA synthetase. J Lip Res 37:2288–2295
Wellik DM, Norback DH, DeLuca HF (1997) Retinol is specifically required during midgestation for neonatal survival. Am J Physiol 272: E25-E29
White JA, Guo YD, Baetz K, Beckett-Jones B, Bonasoro J, Hsu KE, Dilworth FJ, Jones G, Petkovich M (1996) Identification of the retinoic acid-inducible all-trans-retinoic acid 4-hydroxylase. J Biol Chem 271:29922–29927
Wilson JG, Roth CB, Warkany (1953) An analysis of the syndrome of malfunctions induced by maternal vitamin A deficiency. Effects of restoration of vitamin A at various times during gestation. Am J Anat 92:189–217
Yamagata T, Momoi MY, Yanagisawa M, Kumagai H, Yamakado M, Momoi T (1994) Changes of the expression and distribution of retinoic acid receptors during neurogenesis in mouse embryos. Dev Brain Res 77:163–176
Zhang XK, Lehmann J, Hoffmann B, Dawson MI, Cameron J, Graupner G, Hermann T, Tran P, Pfahl M (1992) Homodimer formation of retinoid X-receptor induced by 9-cis retinoic acid. Nature 358:587–591
Zhang XK, Pfahl M (1993) Regulation of retinoid and thyroid hormone action through homodimeric and heterodimeric receptors. Trends Endocrinol Metab 4:156–162
Zile MH (1998) Vitamin A and embryonic development: an overview. J Nutr 128:455S–458S
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Nau, H., Elmazar, M.M.A. (1999). Retinoid Receptors, Their Ligands, and Teratogenesis: Synergy and Specificity of Effects. In: Nau, H., Blaner, W.S. (eds) Retinoids. Handbook of Experimental Pharmacology, vol 139. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58483-1_16
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