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First published online 21 November 2007
doi: 10.1242/dev.009951
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1 GSF-National Research Institute for Environment and Health, Institute for Stem
Cell Research, Ingolstädter Landstr. 1, 85764 Neuherberg/Munich,
Germany.
2 Physiological Genomics, University of Munich, Schillerstr. 46, 80639 Munich,
Germany.
* Author for correspondence (e-mail: Magdalena.goetz{at}gsf.de)
Accepted 23 September 2007
The size of brain regions depends on the balance between proliferation and
differentiation. During development of the mouse cerebral cortex, ventricular
zone (VZ) progenitors, neuroepithelial and radial glial cells, enlarge the
progenitor pool by proliferative divisions, while basal progenitors located in
the subventricular zone (SVZ) mostly divide in a differentiative mode
generating two neurons. These differences correlate to the existence of an
apico-basal polarity in VZ, but not SVZ, progenitors. Only VZ progenitors
possess an apical membrane domain at which proteins of the Par complex are
strongly enriched. We describe a prominent decrease in the amount of
Par-complex proteins at the apical surface during cortical development and
examine the role of these proteins by gain- and loss-of-function experiments.
Par3 (Pard3) loss-of-function led to premature cell cycle exit, reflected in
reduced clone size in vitro and the restriction of the progeny to the lower
cortical layers in vivo. By contrast, Par3 or Par6 (Pard6
)
overexpression promoted the generation of Pax6+ self-renewing progenitors in
vitro and in vivo and increased the clonal progeny of single progenitors in
vitro. Time-lapse video microscopy revealed that a change in the mode of cell
division, rather than an alteration of the cell cycle length, causes the
Par-complex-mediated increase in progenitors. Taken together, our data
demonstrate a key role for the apically located Par-complex proteins in
promoting self-renewing progenitor cell divisions at the expense of neurogenic
differentiation in the developing cerebral cortex.
Key words: Cortical progenitors, Cell lineage, Cell proliferation, Pax6, Tbr2 (Eomes)
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