Fig. 6. Transition of pluripotent cells and function of Mbd3. Pluripotency (indicated as black shading in cells and embryos) is passed on from the 3.5 dpc ICM to the early epiblast of 4.5 dpc embryos, and then to the late epiblast of 5.5 dpc embryos. During this transition, the expression levels of the listed genes change as shown. Loss of Mbd3 results in misregulation of genes with asterisks at 3.5 dpc and/or 4.5 dpc, followed by failure of epiblast proliferation and proaminiotic cavity formation at 5.5 dpc. Whereas Nanog downregulation occurs between 3.5 and 4.5 dpc, it is not clear whether expression levels increase during ES cell derivation, or whether ES cells are derived from rare Nanog high-expressing cells at 4.5 dpc. Mbd3/NuRD is required for proliferation of ICM cells in vivo and for isolated ICMs to give rise to a proliferating epiblast in the presence of LIF in culture. Mbd3 is also required for lineage commitment in ES cells (Kaji et al., 2006).