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Vol. 25, No. 2-4, 2003
Issue release date: March–August (September 2003)
Section title: Paper
Dev Neurosci 2003;25:162–172
(DOI:10.1159/000072265)

Extrinsic and Intrinsic Factors Governing Cell Fate in Cortical Progenitor Cultures

Irvin D.K. · Dhaka A. · Hicks C. · Weinmaster G. · Kornblum H.I.
Departments of aMolecular and Medical Pharmacology, Pediatrics and bBiological Chemistry, cThe Crump Institute for Molecular Imaging and the Brain Research Institute, UCLA School of Medicine, Los Angeles, Calif., USA

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Article / Publication Details

First-Page Preview
Abstract of Paper

Received: 3/11/2003
Accepted: 4/28/2003
Published online: 9/15/2003

Number of Print Pages: 11
Number of Figures: 5
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE

Abstract

Central nervous system germinal zones contain stem cells that generate both neurons and glia. In the recent past, these cells have been isolated, maintained in a variety of culture systems and used in vitro for subsequent characterization of molecular mechanisms underlying brain development. Factors that govern cell fate choices of these neural stem cells have not been fully elucidated, but recent studies suggest that age at the time of culture is an important intrinsic mechanism. Stem cell mitogens and Notch-DSL signaling are significant extrinsic factors. In the current study, we compare neurosphere cultures propagated from animals on embryonic day 12, embryonic day 18 and the day of birth and stimulated to divide by either basic fibroblast growth factor (bFGF) or transforming growth factor-α (TGF-α). As described for other systems, when bFGF was used, clonal neurospheres derived from the youngest age gave rise to a greater percentage of neurons. When TGF-α, acting via the epidermal growth factor receptor, was used, this effect was not observed, with neurospheres from younger animals giving rise to a similar percentage of neurons as those derived from older animals suggesting that this growth factor was either stimulating a different population of stem cells to proliferate, or that it was capable of overriding intrinsic mechanisms. Other differences were also observed when the two growth factors were compared, including age-dependent differences in the numbers of putative astrocytes and oligodendrocytes formed. We further assessed age-dependent influences on cell fate by assessing the effects of a lentivirally transduced constitutively activated Notch receptor on cell fate. At all ages studied, Notch activation resulted in a significantly greater number of GFAP-positive cells, seemingly overriding the greater neurogenic potential of younger stem cells. These data suggest that both extrinsic and intrinsic factors differentially regulate cell fate choices of progenitors during cortical development.


Article / Publication Details

First-Page Preview
Abstract of Paper

Received: 3/11/2003
Accepted: 4/28/2003
Published online: 9/15/2003

Number of Print Pages: 11
Number of Figures: 5
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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