Cardiovascular Toxicology

, Volume 2, Issue 1, pp 25–39 | Cite as

Retinoids and cardiovascular developmental defects

Article

Abstract

Vitamin A and related retinoids are critical regulators of normal cardiovascular development. Extreme variations in retinoid levels, too little or too much, dramatically alter embryonic morphogenesis that has teratogenic consequences, including effects on the heart and great vessels. Specific cardiovascular targets of retinoid action include effects on the anteroposterior patterning of the early heart, left-right decisions and cardiac situs, endocardial cushion formation, and, in particular, the neural crest. The cardiovascular defects produced are remarkably similar in deficiency and excess, suggesting modulation of common developmental or cellular processes by different levels of retinoids. The isolation of nuclear receptors that mediate retinoid action has led to the identification of some genes directly involved in the regulation of these processes and other gene products that may be affected more indirectly. This review will examine the mechanism of retinoid action, the requirements for vitamin A during normal heart development, and the consequences of nonphysiologic or teratogenic exposure.

Key Words

Vitamin A retinoic acid teratogenesis heart malformations embryo 

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References

  1. 1.
    Hale, F. (1933). Pigs born without eyeballs. J. Hered. 24: 105–106.Google Scholar
  2. 2.
    Hale, F. (1935). Relation of vitamin A to anophthalmos in pigs. Am. J. Ophthalmol. 18:1087–1093.Google Scholar
  3. 3.
    Blomhoff, R. (1994). Vitamin A in Health and Disease. Marcel Decker, New York.Google Scholar
  4. 4.
    Morriss-Kay, G.M. and Ward, S.J. (1999). Retinoids and mammalian development. Int. Rev. Cytol. 188:73–131.PubMedGoogle Scholar
  5. 5.
    Cohlan, S.Q. (1953). Excessive intake of vitamin A during pregnancy as a cause of congenital anomalies in the rat. Science 117:535.PubMedGoogle Scholar
  6. 6.
    Kochhar, D.M. (1967). Teratogenic activity of retinoic acid. Acta. Pathol. Microbiol. Scand. 70:398–404.PubMedGoogle Scholar
  7. 7.
    Nau, H., Chahoud, I., Dencker, L., Lammer, E.J., and Scott, W.J. (1994). Teratogenicity of vitamin A and retinoids, in Vitamin A in Health and Disease (R. Blumhoff, ed.), pp. 615–664, Marcel Dekker, New York.Google Scholar
  8. 8.
    Lammer, E.J., Chen, D.T., Hoar, R.M., et al. (1985). Retinoic acid embryopathy. N. Engl. J. Med. 313:837–841.PubMedCrossRefGoogle Scholar
  9. 9.
    Miller, R.K., Hendrickx, A.G., Mills, J.L., Hummler, H., and Wiegand, U.W. (1998). Periconceptional vitamin A use: how much is teratogenic? Reprod. Toxicol. 12:75–88.PubMedGoogle Scholar
  10. 10.
    Shenefelt, R.E. (1972). Morphogenesis of malformations in hamsters caused by retinoic acid: relation to dose and stage at treatment. Teratology 5:103–118.PubMedGoogle Scholar
  11. 11.
    Irie, K., Ando, M., and Takao, A. (1990). All-trans retinoic acid induced cardiovascular malformations, in Embryonic Origins of Defective Heart Development (D.E. Bockman and M.L. Kirby, eds.), pp. 387–388, New York Academy of Science, New York.Google Scholar
  12. 12.
    Dai, W.S., LaBraico, J.M., and Stern, R.S. (1992). Epidemiology of isotretinoin exposure during pregnancy. J. Am. Acad. Dermatol. 26:599–606.PubMedCrossRefGoogle Scholar
  13. 13.
    Collins, M.D. and Mao, G.E. (1999). Teratology of retinoids. Annu. Rev. Pharmacol. Toxicol. 39:399–430.PubMedGoogle Scholar
  14. 14.
    Wilson, J.G. and Warkany, J. (1949). Aortic-arch and cardiac anomalies in the offspring of vitamin A deficient rats. Am. J. Anat. 85:113–155.PubMedGoogle Scholar
  15. 15.
    Kalter, H. and Warkany, J. (1961). Experimental production of congenital malformations in strains of inbred mice by maternal treatment with hypervitaminosis A. Am. J. Pathol. 38:1–21.PubMedGoogle Scholar
  16. 16.
    Fishman, M.C. and Chien, K.R. (1997). Fashioning the vertebrate heart: earliest embryonic decisions. Development 124:2099–2117.PubMedGoogle Scholar
  17. 17.
    Sissman, N.J. (1970). Developmental landmarks in cardiac morphogenesis: comparative chronology. Am. J. Cardiol. 25:141–148.PubMedGoogle Scholar
  18. 18.
    Dersch, H. and Zile, M.H. (1993). Induction of normal cardiovascular development in the vitamin A-deprived quail embryo by natural retinoids. Dev. Biol. 160:424–433.PubMedGoogle Scholar
  19. 19.
    Morriss-Kay, G.M. and Sokolova, N. (1996). Embryonic development and pattern formation. FASEB J. 10:961–968.PubMedGoogle Scholar
  20. 20.
    Stainier, D.Y. and Fishman, M.C. (1992). Patterning the zebrafish heart tube: acquisition of anteroposterior polarity. Dev. Biol. 153:91–101.PubMedGoogle Scholar
  21. 21.
    Osmond, M.K., Butler, A.J., Voon, F.C., and Bellairs, R. (1991). The effects of retinoic acid on heart formation in the early chick embryo. Development 113:1405–1417.PubMedGoogle Scholar
  22. 22.
    Yutzey, K.E., Rhee, J.T., and Bader, D. (1994). Expression of the atrial-specific myosin heavy chain AMHC1 and the establishment of anteroposterior polarity in the developing chicken heart. Development 120:871–883.PubMedGoogle Scholar
  23. 23.
    Dickman, E.D. and Smith, S.M. (1996). Sefective regulation of cardiomyocyte gene expression and cardiac morphogenesis by retinoic acid. Dev. Dynam. 206:39–48.Google Scholar
  24. 24.
    Kalter, H. (1959). Hypervitaminosis A-induced internal congenital malformations in strains of inbred mice. Anat. Rec. 134:589.Google Scholar
  25. 25.
    Taylor, I.M., Wiley, M.J., and Agur, A. (1980). Retinoic acid-induced heart malformations in the hamster. Teratology 21:193–197.PubMedGoogle Scholar
  26. 26.
    Leid, M., Kastner, P. and Chambon, P. (1992). Multiplicity generates diversity in the retinoic acid signaling pathways. Trends Biochem. Sci. 17:427–433.PubMedGoogle Scholar
  27. 27.
    Chambon, P. (1996). A decade of molecualar biology of retinoic acid receptors. FASEB J. 10:940–954.PubMedGoogle Scholar
  28. 28.
    Luo, J., Pasceri, P., Conlon, R.A., Rossant, J., and Giguere, V. (1995). Mice lacking all isoforms of retinoic acid receptor beta develop normally and are susceptible to the teratogenic effects of retinoic acid. Mech. Dev. 53:61–71.PubMedGoogle Scholar
  29. 29.
    Iulianella, A. and Lohnes, D. (1997). Contribution of retinoic acid receptor gamma to retinoid-induced craniofacial and axial defects. Dev. Dynam. 209:92–104.Google Scholar
  30. 30.
    Sucov, H.M., Izpisua-Belmonte, J.C., Ganan, Y., and Evans, R.M. (1995). Mouse embryos lacking RXR alpha are resistant to retinoic-acid-induced limb defects. Development 121:3997–4003.PubMedGoogle Scholar
  31. 31.
    Mangelsdorf, D.J., Kliewer, S.A., Kakizuka, A., Umesono, K., and Evans, R.M. (1993). Retinoid receptors. Recent Prog. Horm. Res. 48:99–121.PubMedGoogle Scholar
  32. 32.
    de The, H., del Mar Vivanco-Ruiz, M., Tiollais, P., Stunnenberg, H., and Dejean, A. (1990). Identification of a retinoic acid responsive element in the retinoic acid receptor β gene. Nature 343:177–180.PubMedGoogle Scholar
  33. 33.
    Kurokawa R., Soderstrom, M., Horlein, A., et al. (1995). Polarity-specific activities of retinoic a cid receptors determined by a co-repressor. Nature 377:451–454.PubMedGoogle Scholar
  34. 34.
    Chen, J.D. and Evans, R.M. (1995). A transcriptional corepressor that interacts with nuclear hormone receptors. Nature 377:454–457.PubMedGoogle Scholar
  35. 35.
    Heinzel, T., Lavinsky, R.M., Mullen, T.M., et al. (1997). A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature 387:43–48.PubMedGoogle Scholar
  36. 36.
    Nagy, L., Kao, H.Y., Chakravarti, D., et al. (1997). Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell 89:373–380.PubMedGoogle Scholar
  37. 37.
    Robyr, D. and Wolffe, P. (1998). Hormone action and chromatin remodeling. Cell. Mol. Life Sci. 54:113–124.PubMedGoogle Scholar
  38. 38.
    Yao, T.P., Oh, S.P., Fuchs, M., et al. (1998). Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93:361–372.PubMedGoogle Scholar
  39. 39.
    Shikama, N., Lon, J., and La Thanue, N. (1997). The p300/CBP family integrating signals with transcription factors and chromatin. Trends Cell Biol. 7:230–236.Google Scholar
  40. 40.
    Aranda, A. and Pascual, A. (2001). Nuclear hormone receptors and gene expression. Physiol. Rev. 81:1269–1304.PubMedGoogle Scholar
  41. 41.
    Glass, C.K. and Rosenfeld, M.G. (2000). The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 14:121–141.PubMedGoogle Scholar
  42. 42.
    Kastner, P., Mark, M., and Chambon, P. (1995). Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life? Cell 83:859–869.PubMedGoogle Scholar
  43. 43.
    Lohnes, D., Mark, M., Mendelsohn, C., et al. (1994). Function of the retinoic acid receptors (RARs) during development. (I) Craniofacial and skeletal abnormalities in RAR double mutants. Development 120:2733–2748.Google Scholar
  44. 44.
    Mendelsohn, C., Lohnes, D., Decimo, D., et al. (1994). 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.PubMedGoogle Scholar
  45. 45.
    Sucov, H.M., Dyson, E., Gumeringer, C.L., Price, J., Chien, K.R., and Evans, R.M. (1994). RXR alpha mutant mice establish a genetic basis for vitamin A signaling in heart morphogenesis. Genes Dev. 8:1007–1018.PubMedGoogle Scholar
  46. 46.
    Kastner, P., Grondona, J.M., Mark, M., et al. (1994). Genetic analysis of RXR alpha developmental function: convergence of RXR and RAR signaling pathways in heart and eye morphogenesis. Cell 78:987–1003.PubMedGoogle Scholar
  47. 47.
    Kastner, P., Messaddeq, N., Mark, M., et al. (1997). Vitamin A deficiency and mutations of RXRalpha, RXRbeta and RARalpha lead to early differentiation of embryonic ventricular cardiomyocytes. Development 124:4749–4758.PubMedGoogle Scholar
  48. 48.
    Tran, C.M. and Sucov, H.M. (1998). The RXRalpha gene functions in a non-cell-autonomous manner during mouse cardiac morphogenesis. Development 125:1951–1956.PubMedGoogle Scholar
  49. 49.
    Chen, J., Kubalak, S.W., and Chien, K.R. (1998). Ventricular muscle-restricted targeting of the RXRalpha gene reveals a non-cell-autonomous requirement in cardiac chamber morphogenesis. Development 125:1943–1949.PubMedGoogle Scholar
  50. 50.
    Xavier-Neto, J., Shapiro, M.D., Houghton, L., and Rosenthal, N. (2000). Sequential programs of retinoic acid synthesis in the myocardial and epicardial layers of the developing avian heart. Dev. Biol. 219:129–141.PubMedGoogle Scholar
  51. 51.
    Moss, J.B., Xavier-Neto, J., Shapiro, M.D., et al. (1998). Dynamic patterns of retinoic acid synthesis and response in the developing mammalian heart. Dev. Biol. 199:55–71.PubMedGoogle Scholar
  52. 52.
    Gruber, P.J., Kubalak, S.W., Pexieder, T., Sucov, H.M., Evans, R.M., and Chien, K.R. (1996). RXR alpha deficiency confers genetic susceptibility for aortic sac, conotruncal, atrioventricular cushion, and ventricular muscle defects in mice. J. Clin. Invest. 98:1332–1343.PubMedGoogle Scholar
  53. 53.
    Lee, R.Y., Luo, J., Evans, R.M., Giguere, V., and Sucov, H.M. (1997). Compartment-selective sensitivity of cardiovascular morphogenesis to combinations of retinoic acid receptor gene mutations. Circ. Res. 90:757–764.Google Scholar
  54. 54.
    Dupe, V., Ghyselinck, N.B., Wendling, O., Chambon, P., and Mark, M. (1999). Key roles of retinoic acid receptors alpha and beta in the patterning of the caudal hindbrain, pharyngeal arches and otocyst in the mouse. Development 126:5051–5059.PubMedGoogle Scholar
  55. 55.
    Xavier-Neto, J., Neville, C.M., Shapiro, M.D. et al. (1999). A retinoic acid-inducible transgenic marker of sino-atrial development in the mouse heart. Development 126:2677–2687.PubMedGoogle Scholar
  56. 56.
    Yutzey, K., Gannon, M., and Bader, D. (1995). Diversification of cardiomyogenic cell lineages in vitro. Dev. Biol. 170:531–541.PubMedGoogle Scholar
  57. 57.
    Chazaud, C., Chambon, I., and Dolle, P. (1999). Retinoic acid is required in the mouse embryo for left-right asymmetry determination and heart morphogenesis. Development 126:2589–2596.PubMedGoogle Scholar
  58. 58.
    Niederreither, K., Subbarayan, V., Dolle, P., and Chambon, P. (1999). Embryonic retinoic acid synthesis is essential for early mouse post-implantation. Development Nat. Genet. 21:444–448.Google Scholar
  59. 59.
    Niederreither, K., Vermot, J., Messaddeq, N., Schuhbaur, B., Chambon, P., and Dolle, P. (2001). Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse. Development 128:1019–1031.PubMedGoogle Scholar
  60. 60.
    Tsukui, T., Capdevila, J., Tamura, K., et al. (1999). Multiple left-right asymmetry defects in Shh(−/−) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1. Proc. Natl. Acad. Sci. USA 96:11,376–11,381.Google Scholar
  61. 61.
    Perz-Edwards, A., Hardison, N.L., and Linney, E. (2001). Retinoic acid-mediated gene expression in transgenic reporter zebrafish. Dev. Biol. 229:89–101.PubMedGoogle Scholar
  62. 62.
    Twal, W., Roze, L., and Zile, M.H. (1995). Anti-retinoic acid monoclonal antibody localizes all-trans-retinoic acid in target cells and blocks normal development in early quail embryo. Dev. Biol. 168:225–234.PubMedGoogle Scholar
  63. 63.
    Chen, Y. and Solursh, M. (1992). Comparison of Hensen's node and retinoic acid in secondary axis induction in the early chick embryo. Dev. Dynam. 195:142–151.Google Scholar
  64. 64.
    Smith, S.M., Dickman, E.D., Thompson, R.P., Sinning, A.R., Wunsch, A.M., and Markwald, R.R. (1997). Retinoic acid directs cardiac laterality and the expression of early markers of precardiac asymmetry. Dev. Biol. 182:162–171.PubMedGoogle Scholar
  65. 65.
    Miura, S., Miyagawa, S., Morishima, M., Ando, M., and Takao, A. (1990). Retinoic acid-induced visceroatrial heterotaxy syndrome in rat embryos, in Developmental Cardiology: Morphogenesis and Function (E.B. Clark and A. Takao, eds.), pp. 467–484, Futura, Mt. Kisco, NY.Google Scholar
  66. 66.
    Wasiak, S. and Lohnes, D. (1999). Retinoic acid affects left-right patterning. Dev. Biol. 215:332–342.PubMedGoogle Scholar
  67. 67.
    Yost, H.J. (1999). Establishing cardiac left-right aymmetry, in Heart Development (R.P. Harvey and N. Rosenthal, eds.), pp. 373–402. Academic, San Diego, CA.Google Scholar
  68. 68.
    Burdine, R.D. and Schier, A.F. (2000). Conserved and divergent mechanisms in left-right axis formation. Genes Dev. 14:763–776.PubMedGoogle Scholar
  69. 69.
    Bisgrove, B.W. and Yost, H.J. (2001). Classification of left-right patterning defects in zebrafish, mice, and humans. Am. J. Med. Genet. 101:315–323.PubMedGoogle Scholar
  70. 70.
    Meno, C., Shimono, A., Saijoh, Y., et al. (1998). Tefty-1 is required for left-right determination as a regulator of lefty-2 and nodal. Cell 94:287–297.PubMedGoogle Scholar
  71. 71.
    Norris, D.P. and Robertson, E.J. (1999). Asymmetric and node-specific nodal expression patterns are controlled by two distinct cis-acting regulatory elements. Genes Dev. 13:1575–1588.PubMedGoogle Scholar
  72. 72.
    Oulad-Abdelghani, M., Chazaud, C., Bouillet, P., Mattei, M.G., Dolle, P., and Chambon, P. (1998). Stra3/lefty, a retinoic acid-inducible novel member of the transforming growth factor-beta superfamily. Int. J. Dev. Biol. 42:23–32.PubMedGoogle Scholar
  73. 73.
    Hogan, B.L., Thaller, C., and Eichele, G. (1992). Evidence that Hensen's node is a site of retinoic acid synthesis. Nature 359:237–241.PubMedGoogle Scholar
  74. 74.
    Ray, W.J., Bain, G., Yao, M., and Gottlieb D.I. (1997). CYP26, a novel mammalian cytochrome P450, is induced by retinoic acid and defines a new family. J. Biol. Chem. 272:18,702–18,708.Google Scholar
  75. 75.
    Ruberte, E., Dolle, P., Krust, A., Zelent, A., Morriss-Kay, G., and Chambon, P. (1990). Specific spatial and temporal distribution of retinoic acid receptor gamma transcripts during mouse embryogenesis. Development 108:213–222.PubMedGoogle Scholar
  76. 76.
    Dolle, P., Ruberte, E., Kastner, P., et al. (1989). Differential expression of genes encoding α, β and γ retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature 342:702–705.PubMedGoogle Scholar
  77. 77.
    Zile, M.H., Kostetskii, I., Yuan, S., et al. (2000). Retinoid signaling is required to complete the vertebrate cardiac left/right asymmetry pathway. Dev. Biol. 223:323–338.PubMedGoogle Scholar
  78. 78.
    Kim, S.H., Son, C.S., Lee, J.W., Tockgo, Y.C., and Chun, Y.H. (1995). Visceral heterotaxy syndrome induced by retinoids in mouse embryo. J. Korean Med. Sci. 10:250–257.PubMedGoogle Scholar
  79. 79.
    Yasui, H., Morishima, M., Nakazawa, M., and Aikawa E. (1998). Anomalous looping, atrioventricular cushion dysplasia, and unilateral ventricular hypoplasia in the mouse embryos with right isomerism induced by retinoid acid. Anat. Rec. 250:210–219.PubMedGoogle Scholar
  80. 80.
    Yost, H.J. (1990). Inhibition of proteoglycan synthesis eliminates left-right asymmetry in Xenopus laevis cardiac looping. Development 110:865–874.PubMedGoogle Scholar
  81. 81.
    Yost, H.J. (1992). Regulation of vertebrate left-right asymmetries by extracellular matrix. Nature 357:158–161.PubMedGoogle Scholar
  82. 82.
    Tsuda, T., Philp, N., Zile, M.H., and Linask, K.K. (1996). Left-right asymmetric localization of flectin in the extra-cellular matrix during heart looping. Dev. Biol. 173:39–50.PubMedGoogle Scholar
  83. 83.
    Tsuda, T., Majumder, K., and Linask, K.K. (1998). Differential expression of flectin in the extracellular matrix and left-right assymmetry in mouse embryonic heart during looping stages. Dev. Genet. 23:203–214.PubMedGoogle Scholar
  84. 84.
    Bouman, H.G., Broekhuizen, M.L., Baasten, A.M., Gittenberger-De Groot, A.C., and Wenink, A.C. (1995) Spectrum of looping disturbances in stage 34 chicken hearts after retinoid acid treatment. Anat. Rec. 243:101–108.PubMedGoogle Scholar
  85. 85.
    Bouman, H.G., Broekhuizen, M.L., Baasten, A.M., Gittenberger-de Groot, A.C., and Wenink, A.C. (1998). Diminished growth of atrioventricular cushion tissue in stage 24 retinoic acid-treated chicken embryos. Dev. Dynam. 213:50–58.Google Scholar
  86. 86.
    Yasui, H., Nakazawa, M., Morishima, M., Miyagawa-Tomita, S., and Momma, K. (1995). Morphological observations on the pathogenetic process of transposition of the great arteries induced by retinoic acid in mice. Circulation 91:2478–2486.PubMedGoogle Scholar
  87. 87.
    Nakajima, Y., Hiruma, T., Nakazawa, M., and Morishima, M. (1996). Hypoplasia of cushionidges in the proximal outflow tract elicits formation of right ventricle-to-aortic route in retinoic acid-induced complete transposition of the great arteries in the mouse: scanning electron microscopic observations of corrosion cast models. Anat. Rec. 245:76–82.PubMedGoogle Scholar
  88. 88.
    Nakajima, Y., Morishima, M., Nakazawa, M., Momma, K., and Nakamura, H. (1997). Distribution of fibronectin, type I collagen, type IV collagen, and laminin in the cardiac of the mouse embryonic heart with retinoic acid-induced complete transposition of the great arteries. Anat. Rec. 249:478–485.PubMedGoogle Scholar
  89. 89.
    Yasui, H., Nakazawa, M., Morishima, M., and Aikawa, E. (1997). Altered distribution of collagen type I and hyaluronic acid in the cardiac outflow tract of mouse embryos destined to develop transposition of the great arteries. Heart Vessels 12:171–178.PubMedGoogle Scholar
  90. 90.
    Runyan, R.B. and Markwald, R.R. (1983). Invasion of mesenchyme into three-dimensional collagen gels: a regional and temporal analysis of interaction in embryonic heart tissue. Dev. Biol. 95:108–114.PubMedGoogle Scholar
  91. 91.
    Mjaatvedt, C.H., Yamamura, H., Wessels, A., Ramsdale, A., Turner, D., and Markwald, R.R. (1999). Mechanisms of segmentation, septation and remodeling of the tubular heart: endocardial cushion fate and cardiac looping. in Heart Development (R.P. Harvey and N. Rosenthal, eds.), pp. 159–178. Academic, San Diego, CA.Google Scholar
  92. 92.
    Nakajima, Y., Morishima, M., Nakazawa, M., and Momma, K. (1996). Inhibition of outflow cushion mesenchyme formation in retinoic acid-induced complete transposition of the great arteries. Cardiovasc. Res. 31 Spec No: E77-E85.PubMedGoogle Scholar
  93. 93.
    Yan, M., Nick, T.G., and Sinning, A.R. (2000). Retinoic acid inhibition of cardiac mesenchyme formation in vitro correlates with changes in the secretion of particulate matrix from the myocardium. Anat. Rec. 258:186–197.PubMedGoogle Scholar
  94. 94.
    Balkan, W., Klintworth, G.K., Bock, C.B., and Linney, E. (1992). Transgenic mice expressing a constitutively active retinote acid receptor in the lens exhibit ocular defects. Dev. Biol. 151:622–625.PubMedGoogle Scholar
  95. 95.
    Cash, D.E., Bock, C.B., Schughart, K., Linney, E., and Underwood, T.M. (1997). Retinoic acid receptor a function in vertebrate limb skeletogenesis: a modulator of chondrogenesis. J. Cell. Biol. 136:445–457.PubMedGoogle Scholar
  96. 96.
    Colbert, M.C., Hall, D.G., Kimball, T.R., Witt, S.A., Lorenz, J.N., Kirby, M.L., et al. (1997). Cardiac compartment-specific overexpression of a modified retinoic acid receptor produces dilated cardiomyopathy and congestive heart failure in transgenic mice. J. Clin. Invest. 100:1958–1968.PubMedGoogle Scholar
  97. 97.
    Subbarayan, V., Mark, M., Messadeq, N., Rustin, P., Chambon, P., and Kastner, P. (2000). RXRα overexpression in cardiomyocytes causes dilated cardiomyopathy but fails to rescue myocardial hypoplasia in RXRα-null fetuses. J. Clin. Invest. 105:387–394.PubMedCrossRefGoogle Scholar
  98. 98.
    Kirby, M.L., Gale, T.F., and Stewrt, D.E. (1983). Neural crest cells contribute to normal aorticopulmonary septation. Science 220:1059–1061.PubMedGoogle Scholar
  99. 99.
    LeDouarin, N.M. and Kalcheim, G. (1999). The Neural Crest. Cambridge University Press, Cambridge.Google Scholar
  100. 100.
    Fukiishi Y. and Morriss-Kay, G.M. (1992). Migration of cranial neural crest cells to the pharyngeal arches and heart in rat embryos. Cell Tissue Res. 268:1–8.PubMedGoogle Scholar
  101. 101.
    Tan, S.S., and Morriss-Kay, G. (1985). The development and distribution of the cranial neural crest in the rat embryo. Cell Tissue Res. 240:403–416.PubMedGoogle Scholar
  102. 102.
    Tan, S.S. and Morriss-Kay, G.M. (1986). Analysis of cranial neural crest cell migration and early fates in postimplantation rat chimaeras. J. Embryol. Exp. Morphol. 98:21–58.PubMedGoogle Scholar
  103. 103.
    Morriss-Kay, G., Ruberte, E., and Fukiishi, Y. (1993). Mammalian neural crest and neural crest derivatives. Anat. Anz. 175:501–507.Google Scholar
  104. 104.
    Kirby, M.L. and Waldo, K.L. (1995). Neural crest and cardiovascular patterning. Circ. Res. 77:211–215.PubMedGoogle Scholar
  105. 105.
    Creazzo, T.L., Godt, R.E., Leatherbury, L., Conway, S.J., and Kirby, M.L. (1998). Role of cardiac neural crest cells in cardiovascular development. Annu. Rev. Physiol. 60: 267–286.PubMedGoogle Scholar
  106. 106.
    Maden, M., Graham, A., Gale, E., Rollinson, C., and Zile, M. (1997). Positional apoptosis during vertebrate CNS development in the absence of endogenous retinoids. Development 124:2799–2805.PubMedGoogle Scholar
  107. 107.
    Dickman, E.D., Thaller, C., and Smith, S.M. (1997). Temporally-regulated retinoic acid depletion produces specific neural crest, ocular and nervous system defects. Development 124:3111–3121.PubMedGoogle Scholar
  108. 108.
    White, J.C., Shankar, V.N., Highland, M., Epstein, M.L., DeLuca, H.F., and Clagett-Dame, M. (1998). Defects in embryonic hindbrain development and fetal resorption resulting from vitamin A deficiency in the rat are prevented by feeding pharmacological levels of all-trans-retinoic acid. Proc. Natl. Acad. Sci. USA 95:13,459–13,464.Google Scholar
  109. 109.
    White, J.C., Highland, M., and Clagett-Dame, M. (2000). Abnormal development of the sinoatrial venous valve and posterior hindbrain may contribute to late fetal resorption of vitamin A-deficient rat embryos. Teratology 62:374–384.PubMedGoogle Scholar
  110. 110.
    Wendling, O., Dennefeld, C., Chambon, P., and Mark, M. (2000). Retinoid signaling is essential for patterning the endoderm of the third and fourth pharyngeal arches. Development 127:1553–1562.PubMedGoogle Scholar
  111. 111.
    Ghatpande, S., Ghatpande, A., Zile, M., and Evans, T. (2000). Anterior endoderm is sufficient to rescue foregut apoptosis and heart tube morphogenesis in an embryo lacking retinoic acid. Dev. Biol. 219:59–70.PubMedGoogle Scholar
  112. 112.
    Salvarezza, S. and Rovasio, R. (1997). Exogenous retinoic acid decreases in vivo and in vitro proliferative activity during the early migratory stages of neural crest cells. Cell Prolif. 30:71–80.PubMedGoogle Scholar
  113. 113.
    Li, J., Molkentin, J.D., and Colbert, M.C. (2001). Retinoic acid inhibitors cardiac neural crest migration by blocking c-Jun N-terminal kinase activation. Dev. Biol. 232:351–361.PubMedGoogle Scholar
  114. 114.
    Thorogood, P., Smith, L., Nicol, A., McGinty, R., and Garrod, D. (1982). Effects of vitamin A on the behavior of migratory neural crest cells in vitro. J. Cell Sci. 57:331–350.PubMedGoogle Scholar
  115. 115.
    Smith-Thomas, L., Lott, I., and Bronner-Fraser, M (1987). Effects of isotretinoin on the behavior of neural crest cells in vitro. Dev. Biol. 123:276–281.PubMedGoogle Scholar
  116. 116.
    Schatteman, G.C., Motley, S.T., Effmann, E.L., and Bowen-Pope, D.F. (1995). Platelet-derived growth factor receptor alpha subunit deleted Patch mouse exhibits severe cardiovascular dysmorphogenesis. Teratology 51:351–366.PubMedGoogle Scholar
  117. 117.
    Soriano P. (1997). The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites. Development 124:2691–2700.PubMedGoogle Scholar
  118. 118.
    Morrison-Graham, K., Schatteman, G.C., Bork, T., Bowen-Pope, D.F., and Weston, J.A. (1992). A PDGF receptor mutation in the mouse (Patch) perturbs the development of a non-neuronal subset of neural crest-derived cells. Development 115:133–142.PubMedGoogle Scholar
  119. 119.
    Eferl, R, Sibilia, M., Hilberg, F., Fuchbichler, A., Kufferath, I., Guertl, B., et al. (1999). Functions of c-Jun in liver and heart development. J. Cell Biol. 145:1049–1061.PubMedGoogle Scholar
  120. 120.
    Kirby, M.L. (1989). Plasticity and predetermination of mesencephalic and trunk neural crest transplanted into the region of the cardiac neural crest. Dev. Biol. 134:402–412.PubMedGoogle Scholar
  121. 121.
    Mulder, G.B., Manley, N., and Maggio-Price, L. (1998). Retinoic acid-induced thymic abnormalities in the mouse are associated with altered pharyngeal morphology, thymocyte maturation defects, and altered expression of Hoxa3 and Pax1. Teratology 58:263–275.PubMedGoogle Scholar
  122. 122.
    Mulder, G.B., Manley, N., Grant, J., Schmidt, K., Zeng, W., Eckhoff, C., et al. (2000). Effects of excess vitamin A on development of cranial neural crest-derived structures: a neonatal and embryologic study. Teratology 62:214–226.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  1. 1.Division of Molecular Cardiovascular BiologyCincinnati Children's Hospital Medical CenterCincinnati

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