Expression patterns of Notch1, Notch2, and Notch3 suggest multiple functional roles for the Notch-DSL signaling system during brain development

The Notch-DSL signaling system consists of multiple receptors and ligands, and plays many roles in development. The function of Notch receptors and li gands in mammalian brain, however, is poorly understood. In the current stu dy, we examined the expression patterns for three receptors of this system, Notch1, 2, and 3, in late embryonic and postnatal rat brain by in situ hyb ridization. The three receptors have overlapping but different patterns of expression. Messenger RNA for all three proteins is found in postnatal cent ral nervous system (CNS) germinal zones and, in early postnatal life, withi n numerous cells throughout the CNS. Within zones of cellular proliferation of the postnatal brain, Notch1 mRNA is found in both the subventricular an d the ventricular germinal zones, whereas Notch2 and Notch3 mRNAs are more highly localized to the ventricular zones. Both Notch1 and Notch3 mRNAs are expressed along the inner aspect of the dentate gyrus, a site of adult neu rogenesis. Notch2 mRNA is expressed in the external granule cell layer of t he developing cerebellum. In several brain areas, Notch1 and Notch3 mRNAs a re relatively concentrated in white matter, whereas Notch3 mRNA is not. Neu rosphere cultures (which contain CNS stem cells), purified astrocyte cultur es, and striatal neuron-enriched cultures express Notch1 mRNA. However, in these latter cultures, Notch1 mRNA is produced by nestin-containing cells, rather than by postmitotic neurons. Taken together, these results support m ultiple roles for Notch1, 2, and 3 receptor activation during CNS developme nt, particularly during gliogenesis. J. Comp. Neurol. 436:167-181, 2001. (C ) 2001 Wiley-Liss, Inc.