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The transcriptional factor Sox2 and epidermal growth factor receptor (Egfr)‐mediated signaling are both required for self‐renewal of neural precursor cells (NPCs). However, the mechanism by which these factors coordinately regulate this process is largely unknown. Here we show that Egfr‐mediated signaling promotes Sox2 expression, which in turn binds to the  Egfr  promoter and directly upregulates  Egfr  expression. Knockdown of  Sox2  by RNA interference downregulates  Egfr  expression and attenuates colony formation of NPCs, whereas overexpression of  Sox2  elevates  Egfr  expression and promotes NPC self‐renewal. Moreover, the effect of Sox2 on NPC self‐renewal is completely inhibited by AG1478, a specific inhibitor for Egfr; it is also inhibited by LY294002 and U0126, selective antagonists for phosphatidylinositol 3‐kinase (PI3K) and extracellular signal‐regulated kinase (Erk1/2), respectively. Collectively, we conclude that NPC self‐renewal is enhanced through a novel cellular feedback loop with mutual regulation of Egfr and Sox2. S TEM  C ELLS  2010;28:279–286

The Egf Receptor‐Sox2‐Egf Receptor Feedback Loop Positively Regulates the Self‐Renewal of Neural Precursor Cells