Fig. 7
Proposed model for the role of Ezh2 in mouse midbrain development. Ezh2 controls neural progenitor proliferation and brain area identity via direct and indirect mechanisms. Ezh2 regulates cell cycle progression by H3K27me3-mediated repression of negative cell cycle regulators Cdkna2 and Cdkn2c and Wnt/β-catenin signaling inhibitors Wif1 and Dkk2. Also, Ezh2 maintains midbrain identity of cells by suppressing forebrain determinants Foxg1 and Pax6 and by maintaining Wnt/β-catenin signaling, which is essential for the expression of midbrain markers Pax3 and Pax7. Therefore, loss of Ezh2 in the developing mouse midbrain leads to decreased proliferation and precocious cell cycle exit of neural progenitors in addition to a partial loss of midbrain identity and ectopic establishment of forebrain identity