Retinoic acid is required in the mouse embryo for left-right asymmetry determination and heart morphogenesis.
Determination of the left-right position (situs) of visceral organs involves lefty, nodal and Pitx2 genes that are specifically expressed on the left side of the embryo. We demonstrate that the expression of these genes is prevented by the addition of a retinoic acid receptor pan-antagonist to cultured headfold stage mouse embryos, whereas addition of excess retinoic acid leads to their symmetrical expression. Interestingly, both treatments lead to randomization of heart looping and to defects in heart anteroposterior patterning. A time course analysis indicates that only the newly formed mesoderm at the headfold-presomite stage is competent for these retinoid effects. We conclude that retinoic acid, the active derivative of vitamin A, is essential for heart situs determination and morphogenesis.
Chazaud
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Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, BP 163, CU de Strasbourg, France.
Chambon
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Dollé
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D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D055458:Left-Right Determination Factors; D008648:Mesoderm; D051379:Mice; D008822:Mice, Transgenic; D055457:Nodal Protein; D009687:Nuclear Proteins; D051761:Paired Box Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D029867:Xenopus Proteins; D000097577:Homeobox Protein PITX2
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D055458:Left-Right Determination Factors; D055457:Nodal Protein; D009687:Nuclear Proteins; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D029867:Xenopus Proteins; D000097577:Homeobox Protein PITX2; C095572:Hand1 protein, mouse; C526161:LEFTY1 protein, human; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; C526008:Nodal protein, mouse; C097341:helix-loop-helix protein, eHAND; C101485:homeobox protein PITX1; C433629:homeobox protein PITX3