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Notch activation instructs rapid glial differentiation by multipotent neural crest stem cells

Morrison, S. J. and Perez, S. E. and Verdi, J. M. and Hicks, C. and Weinmaster, G. and Anderson, D. J. (2000) Notch activation instructs rapid glial differentiation by multipotent neural crest stem cells. Developmental Biology, 222 (1). p. 232. ISSN 0012-1606. doi:10.1016/S0012-1606(00)80002-0.

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Notch activation has been widely observed to regulate cell fate determination in the nervous system by transiently inhibiting neuronal differentiation, causing progenitors to remain undifferentiated. As expected, Notch activation inhibited neuronal differentiation by neural crest cells in vivo. To study the mechanism we examined the effect of a soluble Notch accurst, Delta-Fc, on neural crest stem cells (NCSCs) that had been isolated by flow-cytometry. Surprisingly, rather than maintaining these stem cells in an uncommitted state, Delta-Fe instructively promoted Schwann (glial) cell differentiation at the expense of neuronal and myofibroblast fates. Delta-Fe increased not only the extent but also the rate of glial marker expression, suggesting that it acts positively as a differentiation-inducing signal. Induction of glial differentiation by Notch was completely dominant to neuronal differentiation induced by the instructive factor BMP2. These data suggest that expression of Notch ligands by differentiating neuroblasts can override BMP2-Induced neurogenesis and promote gliaI differentiation in neighboring cells. Thus, Notch ligand expression may be the switch that ends neuronal differentiation and initiates glial differentiation by neural crest progenitors in developing peripheral nervous system ganglia. More generally, these data suggest, that Notch can act positively as a differentiation-inducing signal for multipotent stem cells.

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Anderson, D. J.0000-0001-6175-3872
Additional Information:© 2000 by Academic Press.
Issue or Number:1
Record Number:CaltechAUTHORS:20150318-103248839
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Official Citation:Abstracts, Developmental Biology, Volume 222, Issue 1, 1 June 2000, Pages 223-283, ISSN 0012-1606, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55887
Deposited By: Ruth Sustaita
Deposited On:18 Mar 2015 19:25
Last Modified:10 Nov 2021 20:51

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