The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface.
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.
Cappello
Silvia
S
GSF, National Research Center for Environment and Health, Institute for Stem Cell Research, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Munich, Germany.
Attardo
Alessio
A
Wu
Xunwei
X
Iwasato
Takuji
T
Itohara
Shigeyoshi
S
Wilsch-Bräuninger
Michaela
M
Eilken
Hanna M
HM
Rieger
Michael A
MA
Schroeder
Timm T
TT
Huttner
Wieland B
WB
Brakebusch
Cord
C
Götz
Magdalena
M
D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage; D005260:Female; D017353:Gene Deletion; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008938:Mitosis / Q000502:physiology; D009417:Nerve Tissue / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D046569:Neuroepithelial Cells / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D020764:cdc42 GTP-Binding Protein