Reelin induces a radial glial phenotype in human neural progenitor cells by activation of Notch-1.

Reelin and Notch-1 signaling pathways have been recently found to be necessary to induce the expression of brain lipid binding protein (BLBP) and to promote the process extension and the maturation of the neuronal progenitors, the radial glial cells. In this study, we report the cross talk between these two pathways. Both in vitro Reelin treatment and overexpression of Notch-1 intracellular domain (NICD) induced BLBP expression and a radial glial phenotype in an immortalized human neural progenitor (HNP) cell line, isolated from the cortex of 14 weeks old fetus. Reelin treatment increased the level of NICD, indicating that Reelin signaling directly activates Notch-1. In addition, reducing NICD release, by inhibiting gamma-secretase activity, inhibited the Reelin-induced radial glial phenotype in human neural progenitor cells. Furthermore, we found that Dab-1, an adaptor protein downstream of Reelin, was co-immunoprecipitated with Notch-1 and NICD. These data indicate that Reelin signaling induces BLBP expression and a radial glial phenotype in human neural progenitor cells via the activation of Notch-1. This study suggest that Reelin signaling may act to fine tune Notch-1 activation to favor the induction of a radial glial phenotype prenataly and would thus offer an insight into how Notch-1 signaling leads to different cellular fates at different developmental stages.