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Published May 26, 2000 | public
Journal Article

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 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.

Additional Information

© 2000 Cell Press. Received January 7, 2000; Revised April 17, 2000. We thank Jeff Nye, Chris Kintner, and J. J. Archelos for providing reagents; Nirao Shah, Paul Sternberg, and Kai Zinn for comments on the manuscript; Gaby Mosconi for laboratory management; and Suzanne Bixby, Chris J. Kubu, Lan Dinh, Hieu Phan, and Ling Wang for technical assistance. Thanks to Rochelle Diamond and Pat Koen of the Caltech Flow-Cytometry Facility, and to Mark Kukuruga of the University of Michigan Flow-cytometry Facility. S. J. M. was initially supported by a fellowship from the American Cancer Society, California Division. This work was supported in part by NIH grant RO1 NS23476 (to D. J. A.). D. J. A. is an Investigator of the Howard Hughes Medical Institute and J. M. V. is a scholar of the Medical Research Council of Canada.

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