Deregulation of Dorsoventral Patterning by FGF Confers Trilineage Differentiation Capacity on CNS Stem Cells In Vitro
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.
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.Attached Files
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Additional details
- Eprint ID
- 55517
- Resolver ID
- CaltechAUTHORS:20150304-113720823
- Damon Runyon Cancer Research Foundation
- Wellcome Trust
- Pritzker Neurogenesis Consortium
- Howard Hughes Medical Institute (HHMI)
- Created
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2015-03-04Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field