Developmental abnormalities in cultured mouse embryos deprived of retinoic by inhibition of yolk-sac retinol binding protein synthesis.
Presomitic and 3- to 12-somite pair cultured mouse embryos were deprived of retinoic acid (RA) by yolk-sac injections of antisense oligodeoxynucleotides for retinol binding protein (RBP). Inhibition of yolk-sac RBP synthesis was verified by immunohistochemistry, and the loss of activity of a lacZ-coupled RA-sensitive promoter demonstrated that embryos rapidly became RA-deficient. This deficiency resulted in malformations of the vitelline vessels, cranial neural tube, and eye, depending upon the stage of embryonic development at the time of antisense injection. Addition of RA to the culture medium at the time of antisense injection restored normal development implicating the role of RBP in embryonic RA synthesis. Furthermore, the induced RA deficiency resulted in early down-regulation of developmentally important genes including TGF-beta1 and Shh.
Båvik
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Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Instutut National de la Santé et de la Recherche Médicale, Universite Louis Pasteur, C.U. de Strasbourg, France.
Ward
S J
SJ
Chambon
P
P
D000818:Animals; D001483:Base Sequence; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D004627:Embryonic Induction; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012177:Retinol-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015534:Trans-Activators; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology*; D015017:Yolk Sac / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure
D053823:Hedgehog Proteins; D016376:Oligonucleotides, Antisense; D012177:Retinol-Binding Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D014212:Tretinoin