In the present study, we aim to elucidate the role of caveolin-1 in modulating astroglial differentiation of neural progenitor cells (NPCs) and the potential mechanisms involved. We first investigated astroglial differentiation and Notch signaling by detecting the expressions of S100 beta, GFAP, NICD and hairy enhancer of split 1 (Hest) in the brains of wild-type and caveolin-1 knockout mice. Caveolin-1 knockout mice revealed remarkably less astroglial differentiation and lower levels of NICD and Hest expressions than wild type mice. We then studied the potential roles of caveolin-1 in modulating NICD and Hes1 expressions and astroglial differentiation in isolated cultured NPCs by using caveolin-1 peptide and caveolin-1 RNA silencing. In the differentiating NPCs, caveolin-1 peptide markedly promoted astroglial formation and up-regulated the expressions of NICD and Hes1. In contrast, the knockdown of caveolin-1 inhibited astroglial differentiation of NPCs and the expressions of NICD and Hest. Taken together, these results provide strong evidence that caveolin-1 can promote astroglial differentiation of NPCs through modulating Notch1/NICD and Hes1 expressions. (C) 2011 Elsevier Inc. All rights reserved.