Notch3 signaling promotes radial glial/progenitor character in the mammalian telencephalon

The Notch signaling pathway is known to influence cell fate in the developing mammalian nervous system. Previous work in the mouse telencephalon has shown that activated Notch1 promotes radial glial and astrocytic character in vivo, and fibroblast growth factor (FGF)-responsive neural progenitor character in vitro. In light of studies suggesting that Notch3 can antagonize Notch1, we tested the effects of activated Notch3 (NICD3) in the mouse telencephalon. Infection of embryonic day 9.5 telencephalic progenitors in vivo with NICD3 promoted radial glial/progenitor character embryonically and astrocyte fate postnatally. In addition, expression of NICD3 in telencephalic progenitors in vitro increased neurosphere frequency in FGF2, but was incompatible with neurosphere growth in epidermal growth factor (EGF). Thus, in the developing telencephalon, Notch1 and Notch3 function similarly, and may activate similar signaling cascades. Consistent with this notion, expression of an activated form of the Notch effector CBF1 (CBF1-VP16), or of the pathway target Hes5 promoted radial glial/progenitor character in vivo. Interestingly, unlike NICD1 and NICD3, CBF1-VP16 and Hes5 did not inhibit neurosphere growth in EGF, suggesting that this effect may be mediated at least in part by CBF1/Hes-independent signaling.