Transient notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells

The genesis of vertebrate peripheral ganglia poses the problem of how multi potent neural crest stem cells (NCSCs) can sequentially generate neurons an d then glia in a local environment containing strong instructive neurogenic factors, such as BMP2. Here we show that Notch ligands, which are normally expressed on differentiating neuroblasts, can inhibit neurogenesis in NCSC s in a manner that is completely dominant to BMP2. Contrary to expectation, Notch activation did not maintain these stem cells in an uncommitted state or promote their self-renewal. Rather, even a transient activation of Notc h was sufficient to cause a rapid and irreversible loss of neurogenic capac ity accompanied by accelerated glial differentiation. These data suggest th at Notch ligands expressed by neuroblasts may act positively to instruct a cell-heritable switch to gliogenesis in neighboring stem cells.