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Cerebral Cortex Advance Access published online on April 10, 2009
Cerebral Cortex, doi:10.1093/cercor/bhp046
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Late Origin of Glia-Restricted Progenitors in the Developing Mouse Cerebral Cortex

Marcos R. Costa1,3,4, Oliver Bucholz1, Timm Schroeder1 and Magdalena Götz1,2

1 Institute for Stem Cell Research, Helmholtz Zentrum München, National Research Center for Environment and Health, D-85764 Neuherberg, Germany, 2 Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, D-80336 Munich, Germany

Address correspondence to email: mrcosta{at}propesq.ufrn.br.

In order to unravel the molecular determinants of cell fate, it is important to understand when fate restriction occurs during brain development. Lineage analysis suggested that bi- or multipotent progenitors persist into late developmental stages in some central nervous system regions, whereas most progenitor cells in the cerebral cortex appeared to be restrained to generate only a single cell type already at early stages. Here we discuss this previous work and present new data demonstrating that cortical progenitors generating exclusively glial cells appear late in development. In utero transduction of cortical progenitors at early and mid-neurogenesis using a combination of replication-defective retroviral vectors encoding different fluorescent proteins indicated that the early developing cortex is devoid of glia-restricted progenitors, although these are frequent during mid- and late neurogenesis. Clonal analyses in vitro using retroviral vectors and live cell tracking by video time-lapse microscopy confirmed these findings, revealing that the early developing cortex harbors 2 main progenitor types: neuron-restricted and bipotent (neuron–glial) progenitors. The latter are responsible for the generation of glial-restricted progenitors at mid- and late neurogenesis.

Key Words: clonal analysis • cortical development • gliogenesis • neurogenesis • video microscopy

3 Current address: Edmond and Lily Safra International Institute of Neuroscience of Natal, Natal, RN 59066-060, Brazil

4 Current address: Universidade Federal do Rio Grande do Norte, Natal, RN 59072-970, Brazil


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