Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1.
The neural crest (NC) generates a variety of neural and non-neural tissues during vertebrate development. Both migratory NC cells and their target structures contain cells with stem cell features. Here we show that these populations of neural crest-derived stem cells (NCSCs) are differentially regulated by small Rho GTPases. Deletion of either Cdc42 or Rac1 in the NC results in size reduction of multiple NC target structures because of increased cell-cycle exit, while NC cells emigrating from the neural tube are not affected. Consistently, Cdc42 or Rac1 inactivation reduces self-renewal and proliferation of later stage, but not early migratory NCSCs. This stage-specific requirement for small Rho GTPases is due to changes in NCSCs that, during development, acquire responsiveness to mitogenic EGF acting upstream of both Cdc42 and Rac1. Thus, our data reveal distinct mechanisms for growth control of NCSCs from different developmental stages.
Fuchs
Sebastian
S
Institute of Anatomy, University of Zurich, CH-8057 Zurich, Switzerland.
Herzog
Dominik
D
Sumara
Grzegorz
G
Büchmann-Møller
Stine
S
Civenni
Gianluca
G
Wu
Xunwei
X
Chrostek-Grashoff
Anna
A
Suter
Ueli
U
Ricci
Romeo
R
Relvas
João B
JB
Brakebusch
Cord
C
Sommer
Lukas
L
D000483:Alleles; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D011995:Recombination, Genetic; D013234:Stem Cells / Q000201:enzymology*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D004815:Epidermal Growth Factor; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein