Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain

Neural stem cells, which differentiate into neurons and glia, are present i n the ventricular zone of the embryonal brain. The precise mechanism by whi ch neural stem cells are maintained during embryogenesis remains to be dete rmined. Here, we found that transient misexpression of the basic helix-loop -helix genes Hes1 and Hes5 keeps embryonal telencephalic cells undifferenti ated although they have been shown to induce gliogenesis in the retina. The se telencephalic cells later differentiate into neurons and astroglia when Hes expression is down-regulated, suggesting that Hes1- and Hes5- expressin g cells are maintained as neural stem cells during embryogenesis. Conversel y, in the absence of Hes1 and Hes5, neural stem cells are not properly main tained, generating fewer and smaller neurospheres than the wild type. These results indicate that Hes1 and Hes5 play an important role in the maintena nce of neural stem cells but not in gliogenesis in the embryonal telencepha lon.