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The Journal of Neuroscience, October 17, 2007, 27(42):11376-11388; doi:10.1523/JNEUROSCI.2418-07.2007

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Development/Plasticity/Repair
The Marginal Zone/Layer I as a Novel Niche for Neurogenesis and Gliogenesis in Developing Cerebral Cortex

Marcos R. Costa,1,2,3 Nicoletta Kessaris,4 William D. Richardson,4 Magdalena Götz,1,5 * and Cecilia Hedin-Pereira2,3 *

1National Research Center for Environment and Health, Institute for Stem Cell Research, 85764 Neuherberg/Munich, Germany, 2Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 21941-902, 3Laboratório de Neuroanatomia Celular, Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 21941-590, 4Wolfson Institute for Biomedical Research and Department of Biology, University College London, London WC1E 6BT, United Kingdom, and 5Physiological Genomics, Institute of Physiology, University of Munich, 80336 Munich, Germany

Correspondence should be addressed to either Marcos R. Costa or Magdalena Götz, National Research Center for Environment and Health, Institute for Stem Cell Research, Ingolstädt Landstrasse 1, 85764 Neuherberg/Munich, Germany. Email: marcos.costa{at}gsf.de or Email: magdalena.goetz{at}gsf.de

The cellular diversity of the cerebral cortex is thought to arise from progenitors located in the ventricular zone and subventricular zone in the telencephalon. Here we describe a novel source of progenitors located outside these two major germinative zones of the mouse cerebral cortex that contributes to neurogenesis and gliogenesis. Proliferating cells first appear in the preplate of the embryonic cerebral cortex and further increase in the marginal zone during mid and late neurogenesis. The embryonic marginal zone progenitors differ in their molecular characteristics as well as the size and identity of their clonal progeny from progenitors isolated from the ventricular zone and subventricular zone. Time-lapse video microscopy and clonal analysis in vitro revealed that the marginal zone progenitor pool contains a large fraction of oligodendrocyte or astrocyte progenitors, as well as neuronal and bipotent progenitors. Thus, marginal zone progenitors are heterogenous in regard to their fate specification, as well as in regard to their region of origin (pallial and subpallial) as revealed by in vivo fate mapping. The local environment in the marginal zone tightly regulates the size of this novel progenitor pool, because both basement membrane defects in laminin{gamma}1–/– mice or alterations in the cellular composition of the marginal zone in Pax6 Small Eye mutant mice lead to an increase in the marginal zone progenitor pool. In conclusion, we have identified a novel source of neuronal and glial progenitors in the marginal zone of the developing cerebral cortex with properties notably distinct from those of ventricular zone and subventricular zone progenitors.

Key words: marginal zone; cerebral cortex; development; neurogenesis; gliogenesis; Reelin; basement membrane


Received Jan. 19, 2007; revised Aug. 3, 2007; accepted Aug. 16, 2007.

Correspondence should be addressed to either Marcos R. Costa or Magdalena Götz, National Research Center for Environment and Health, Institute for Stem Cell Research, Ingolstädt Landstrasse 1, 85764 Neuherberg/Munich, Germany. Email: marcos.costa{at}gsf.de or Email: magdalena.goetz{at}gsf.de






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