Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate

Notch1 has been shown to induce glia in the peripheral nervous system. Howe ver, it has not been known whether Notch can direct commitment to glia from multipotent progenitors of the central nervous system. Here we present evi dence that activated Notch1 and Notch3 promotes the differentiation of astr oglia from the rat adult hippocampus-derived multipotent progenitors (AHPs) . Quantitative clonal analysis indicates that the action of Notch is likely to be instructive. Transient activation of Notch can direct commitment of AHPs irreversibly to astroglia. Astroglial induction by Notch signaling was shown to be independent of STAT3, which is a key regulatory transcriptiona l factor when ciliary neurotrophic factor (CNTF) induces astroglia. These d ata suggest that Notch provides a CNTF-independent instructive signal of as troglia differentiation in CNS multipotent progenitor cells.