Notch signaling is critical for multiple aspects of neurogenesis, but how it regulates the proliferation and differentiation of neural stem cells (NSCs) and intermediate neural progenitors (INPs) has not been well elucidated, especially in vivo. In this study, we conditionally ablated the transcription factor RBP-J, which mediates signaling fromall fourmammalian Notch receptors, in the basal forebrain and ventralmidbrain using the RBP-J-ﬂoxed mouse and a newly established Nestin-Cre mouse. We found that at early stage of neurogenesis (E11.5), the frequency of neurospheres increased signiﬁcantly in the RBP-J-inactivated regions. The majority of the RBP-J deﬁcient neurospheres were composed of INPs, suggesting the precocious differentiation of NSCs into INPs.Meanwhile, neuronal differentiationwas reduced in the same regions at E11.5, inconsistent with the precocious differentiation phenotype inmost Notch-relatedmutants. At late neurogenic stages (E17.5 and neonatal), as expected from precociously exhausted NSC pool, neurosphere frequency and NSCs decreased in the RBP-J-ablated regions, accompanied by a signiﬁcant increase of both neurons and glial cells. These results indicated that the RBP-J-mediated signaling might inhibit the differentiation of NSCs into INPs and support the generation of certain early born neurons at early neurogenic stages.
下一条：HaiFeng OuYang（Mol. Cell. Biochem2008）