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 developme nt has been extensively studied, little is known about the genetic control of RA teratogenicity, The knockout of the homeobox gene goosecoid in the mo use revealed similarities to RA induced embryopathy, We show that RA treatm ent 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-trea tment as well, both in embryos and in F9 teratocarcinoma cells. Our data su ggest that both goosecoid and BMP-4 function as mediators of RA teratogenic ity in mouse embryos.