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Abstract
The genesis of vertebrate peripheral ganglia poses the problem of how multipotent
neural crest stem cells (NCSCs) can sequentially generate neurons and 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 NCSCs 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 Notch was sufficient to cause a rapid and irreversible loss of neurogenic capacity
accompanied by accelerated glial differentiation. These data suggest that Notch ligands
expressed by neuroblasts may act positively to instruct a cell-heritable switch to
gliogenesis in neighboring stem cells.