The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface.

TY - JOUR

T1 - The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface.

AU - Cappello, Silvia

AU - Attardo, Alessio

AU - Wu, Xunwei

AU - Iwasato, Takuji

AU - Itohara, Shigeyoshi

AU - Wilsch-Bräuninger, Michaela

AU - Eilken, Hanna M

AU - Rieger, Michael A

AU - Schroeder, Timm T

AU - Huttner, Wieland B

AU - Brakebusch, Cord

AU - Götz, Magdalena

N1 - Keywords: Adherens Junctions; Animals; Cell Cycle; Cell Division; Cell Lineage; Female; Gene Deletion; Immunohistochemistry; In Situ Hybridization; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitosis; Nerve Tissue; Neuroepithelial Cells; Stem Cells; Telencephalon; cdc42 GTP-Binding Protein

PY - 2006

Y1 - 2006

N2 - Stem cell persistence into adulthood requires self-renewal from early developmental stages. In the developing mouse brain, only apical progenitors located at the ventricle are self-renewing, whereas basal progenitors gradually deplete. However, nothing is known about the mechanisms regulating the fundamental difference between these progenitors. Here we show that the conditional deletion of the small Rho-GTPase cdc42 at different stages of neurogenesis in mouse telencephalon results in an immediate increase in basal mitoses. Whereas cdc42-deficient progenitors have normal cell cycle length, orientation of cell division and basement membrane contact, the apical location of the Par complex and adherens junctions are gradually lost, leading to an increasing failure of apically directed interkinetic nuclear migration. These cells then undergo mitoses at basal positions and acquire the fate of basal progenitors. Thus, cdc42 has a crucial role at the apical pole of progenitors, thereby regulating the position of mitoses and cell fate.

AB - Stem cell persistence into adulthood requires self-renewal from early developmental stages. In the developing mouse brain, only apical progenitors located at the ventricle are self-renewing, whereas basal progenitors gradually deplete. However, nothing is known about the mechanisms regulating the fundamental difference between these progenitors. Here we show that the conditional deletion of the small Rho-GTPase cdc42 at different stages of neurogenesis in mouse telencephalon results in an immediate increase in basal mitoses. Whereas cdc42-deficient progenitors have normal cell cycle length, orientation of cell division and basement membrane contact, the apical location of the Par complex and adherens junctions are gradually lost, leading to an increasing failure of apically directed interkinetic nuclear migration. These cells then undergo mitoses at basal positions and acquire the fate of basal progenitors. Thus, cdc42 has a crucial role at the apical pole of progenitors, thereby regulating the position of mitoses and cell fate.

U2 - 10.1038/nn1744

DO - 10.1038/nn1744

M3 - Journal article

C2 - 16892058

SN - 1097-6256

VL - 9

SP - 1099

EP - 1107

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 9

ER -