Retinoic acid teratogenicity: the role of goosecoid and BMP-4.
Retinoic acid (RA) plays a pivotal role during vertebrate development, both as morphogen and as potent teratogen. While RA function in axial development has been extensively studied, little is known about the genetic control of RA teratogenicity. The knockout of the homeobox gene goosecoid in the mouse revealed similarities to RA induced embryopathy. We show that RA treatment of mouse gastrula embryos in vitro and of E10.5 embryos in utero led to a rapid but transient down-regulation of goosecoid expression. Repression was dependent on retinoid X receptors (RXR). BMP-4 was repressed by RA-treatment as well, both in embryos and in F9 teratocarcinoma cells. Our data suggest that both goosecoid and BMP-4 function as mediators of RA teratogenicity in mouse embryos.
Zhu
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St. Jude Children's Research Hospital, Memphis, TN 38105-2907, USA.
Yamada
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G
Blum
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D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000187:drug effects / Q000235:genetics*; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005775:Gastrula / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D051956:Goosecoid Protein; D018398:Homeodomain Proteins / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D009924:Organ Culture Techniques; D011247:Pregnancy; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012097:Repressor Proteins; D047488:Retinoid X Receptors; D018243:Teratocarcinoma / Q000188:drug therapy / Q000235:genetics; D013723:Teratogens / Q000633:toxicity*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000633:toxicity*; D014407:Tumor Cells, Cultured
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D051956:Goosecoid Protein; C497993:Gsc protein, mouse; D018398:Homeodomain Proteins; D011506:Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D047488:Retinoid X Receptors; D013723:Teratogens; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014212:Tretinoin