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First published online 21 November 2007
doi: 10.1242/dev.009951

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Par-complex proteins promote proliferative progenitor divisions in the developing mouse cerebral cortex

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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