Notch signaling is involved in a variety of cell-fate decisions during 
development. Here we investigate the role of Notch signaling in apoptotic cell 
death of neural progenitors through the generation and analysis of cell 
type-specific conditional transgenic and knockout mice. We show that conditional 
expression of a constitutively active form of Notch1 in early neural progenitor 
cells, but not postmitotic neurons, selectively induces extensive apoptosis, 
resulting in a markedly reduced progenitor population. Conversely, attenuation 
of Notch signaling in Notch1 conditional knockout or Presenilin-1-/- mice 
results in reduced apoptosis of early neural progenitor cells. Furthermore, 
Notch activation in neural progenitor cells leads to elevated levels of nuclear 
p53 and transcriptional upregulation of the target genes Bax and Noxa, and the 
promotion of apoptotic cell death by Notch activation is completely suppressed 
by p53 deficiency. Together, these complementary gain-of-function and 
loss-of-function studies reveal a previously unappreciated role of Notch 
signaling in the regulation of apoptotic cell death during early mammalian 
neural development.