Loss of Tfap2c leads to developmental defects in the extra-embryonic compartment with embryonic lethality at E7.5. To investigate requirement of Tfap2c in later placental development, deletion of Tfap2c was induced throughout extra-embryonic ectoderm at E6.5 leading to severe placental abnormalities caused by reduced trophoblast population resulting in embryonic retardation by E8.5. Deletion of Tfap2c in Tpbpa(+) progenitors at E8.5 results in growth arrest of junctional zone. TFAP2C regulates its target genes p21/Cdkn1a and Dusp6, involved in repression of MAPK signaling. Loss of TFAP2C reduces activation of ERK1/2 in the placenta. Downregulation of Akt and reduced activation of pAKT in the mutant placenta are accompanied by impaired glycogen synthesis. Loss of Tfap2c led to upregulation of imprinted gene H19 and downregulation of Tex19.1 and Ascl2. The placental insufficiency post E16.5 causes fetal growth restriction with 19% lighter mutant pups. TFAP2C knockdown in human trophoblast choriocarcinoma JAr cells inhibited MAPK and AKT signaling. Thus, we present a model where Tfap2c in trophoblasts controls proliferation by repressing P21 and activating MAPK pathway and further supporting differentiation of glycogen cells via activating Akt pathway.