Notch and NFκB signaling pathways:: do they collaborate in normal vertebrate brain development and function?

Both Notch and NF kappa B signaling pathways are well-known for regulating proliferation, differentiation and apoptosis. Recent studies have presented several lines of evidence supporting an integration of the Notch and NF kappa B signaling pathways in differentiation/maturation of a diverse range of cell types. It is notable that Notch and NF kappa B signaling pathways share many common features: (i) both are activated by common stimuli such as TNF-alpha and hypoxia, (ii) activated Notch (NICD) and NF kappa B mediate transcription by regulating corepressors such as SMRT/N-COR, and (iii) both regulate similar target genes such as Hes-1 and I kappa B alpha. This review expands on how the collaboration between these pathways may play an important role in the CNS. We will speculate on the mechanisms by which Notch and NF kappa B signaling may collaborate to regulate stem cell renewal and differentiation during brain development and function.