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Deregulation of Dorsoventral Patterning by FGF Confers Trilineage Differentiation Capacity on CNS Stem Cells In Vitro

Gabay, Limor and Lowell, Sally and Rubin, Lee L. and Anderson, David J. (2003) Deregulation of Dorsoventral Patterning by FGF Confers Trilineage Differentiation Capacity on CNS Stem Cells In Vitro. Neuron, 40 (3). pp. 485-499. ISSN 0896-6273. doi:10.1016/S0896-6273(03)00637-8. https://resolver.caltech.edu/CaltechAUTHORS:20150304-113720823

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Abstract

The CNS is thought to develop from self-renewing stem cells that generate neurons, astrocytes, and oligodendrocytes. Other data, however, have suggested that astrocytes and oligodendrocytes are generated from separate progenitor populations. To reconcile these observations, we have prospectively isolated progenitors that do or do not express Olig2, an oligodendrocyte bHLH determination factor. Both Olig2− and Olig2+ progenitors can behave as tripotential CNS stem cells (CNS-SCs) in vitro. Growth in FGF-2 causes induction of Olig2 in the former population, permitting oligodendrocyte differentiation; extinction of Olig2 in the latter cells permits astrocyte differentiation. The induction of Olig2 by FGF-2 is mediated, in part, via endogenous Sonic Hedgehog. These data indicate that clonogenic competence to generate neurons, astrocytes, and oligodendrocytes reflects a deregulation of dorsoventral patterning during expansion in vitro, raising the question of whether such trifatent cells actually exist in vivo.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/S0896-6273(03)00637-8DOIArticle
ORCID:
AuthorORCID
Anderson, David J.0000-0001-6175-3872
Additional Information:© 2003 Cell Press. Under an Elsevier user license. Received: July 22, 2003; Revised: September 4, 2003; Accepted: September 16, 2003; Published: October 29, 2003. We thank Ben Novitch and Tom Jessell for providing many antibodies and Olig2-GFP mice in advance of publication and for helpful discussion; Peter Gruss and Martyn Goulding for providing Pax3-laZ mice; Shelley Diamond for help with FACS; Bruce Kennedy and Shirley Pease for managing transgenic mice; and Gaby Mosconi for laboratory management. L.G. was supported by a Damon Runyon fellowship, and S.L. by a Wellcome Trust long-term travelling research fellowship. This work was supported in part by the Pritzker Neurogenesis Research Consortium. D.J.A. is an Investigator of the Howard Hughes Medical Institute.
Funders:
Funding AgencyGrant Number
Damon Runyon Cancer Research FoundationUNSPECIFIED
Wellcome TrustUNSPECIFIED
Pritzker Neurogenesis ConsortiumUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:3
DOI:10.1016/S0896-6273(03)00637-8
Record Number:CaltechAUTHORS:20150304-113720823
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150304-113720823
Official Citation:Gabay, L., Lowell, S., Rubin, L. L., & Anderson, D. J. (2003). Deregulation of Dorsoventral Patterning by FGF Confers Trilineage Differentiation Capacity on CNS Stem Cells In Vitro. Neuron, 40(3), 485-499. doi: http://dx.doi.org/10.1016/S0896-6273(03)00637-8
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55517
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:04 Mar 2015 20:35
Last Modified:10 Nov 2021 20:46

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