JunB is essential for mammalian placentation

Lack of JunB, an immediate early gene product and member of the AP-1 transc ription factor family causes embryonic lethality between E8.5 and E10.0. Al though mutant embryos are severely retarded in growth and development, cell ular proliferation is apparently not impaired. Retardation and embryonic de ath are caused by the inability of JunB-deficient embryos to establish prop er vascular interactions with the maternal circulation due to multiple defe cts in extra-embryonic tissues, The onset of the phenotypic defects correla tes well with high expression of junB in wild-type extra-embryonic tissues. In trophoblasts, the lack of JunB causes a deregulation of proliferin, mat rix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA) g ene expression, resulting in a defective neovascularization of the decidua, As a result of downregulation of the VEGF-receptor 1 (flt-1), blood vessel s in the yolk sac mesoderm appeared dilated, Mutant embryos which escape th ese initial defects finally die from a nonvascularized placental labyrinth Injection of junB(-/-) embryonic stem (ES) cells into tetraploid wild-type blastocysts resulted in a partial rescue, in which the ES cell-derived fetu ses were no longer growth retarded and displayed a normal placental labyrin th, Therefore, JunB appears to be involved in multiple signaling pathways r egulating genes involved in the establishment of a proper fete-maternal cir culatory system.