Developmental abnormalities in cultured mouse embryos deprived of retinoic acid 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 (REP), Inhibition of yolk-sac REP 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 REP in embryonic RA synthesis, Furthermore, the induced RA deficiency resulted in early down-regulation of developmentally important genes including TGF-beta(1) and Shh.