| First Author | Yang MS | Year | 2011 |
| Journal | Biochem Biophys Res Commun | Volume | 404 |
| Issue | 1 | Pages | 133-8 |
| PubMed ID | 21108929 | Mgi Jnum | J:167453 |
| Mgi Id | MGI:4868307 | Doi | 10.1016/j.bbrc.2010.11.080 |
| Citation | Yang MS, et al. (2011) Among gamma-secretase substrates Notch1 alone is sufficient to block neurogenesis but does not confer self-renewal properties to neural stem cells. Biochem Biophys Res Commun 404(1):133-8 |
| abstractText | Notch signaling pathway enhances neural stem cell characters and regulates cell fate decisions during neural development. Interestingly, besides Notch, other gamma-secretase substrates such as APP, LRP2, and ErbB4 have also proven to have biological functions in neural development. We designed a unique experimental setting, combining gain-of- (expression of Notch intracellular domain, NICD) and loss-of-function (gamma-secretase inhibition) methods, and were able to examine the function of Notch alone by excluding the activity of other gamma-secretase substrates. Here, we show that the frequency and size of neurospheres generated from embryonic neural stem cells (NSCs) significantly decreased by 62.7% and 37.2%, respectively, in the presence of gamma-secretase inhibitor even when NICD was expressed. Under the condition of differentiation, however, the gamma-secretase inhibitor treatment did not influence the promotion of astrogenesis at the expense of neurogenesis by NICD. These results indicate that other gamma-secretase substrate(s) along with Notch are important in the maintenance of the stemness of NSCs, but that Notch alone can sufficiently inhibit neurogenesis without the action of the other gamma-secretase substrates during differentiation. |
