WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility.
The Wiskott-Aldrich syndrome related protein WAVE2 is implicated in the regulation of actin-cytoskeletal reorganization downstream of the small Rho GTPase, Rac. We inactivated the WAVE2 gene by gene-targeted mutation to examine its role in murine development and in actin assembly. WAVE2-deficient embryos survived until approximately embryonic day 12.5 and displayed growth retardation and certain morphological defects, including malformations of the ventricles in the developing brain. WAVE2-deficient embryonic stem cells displayed normal proliferation, whereas WAVE2-deficient embryonic fibroblasts exhibited severe growth defects, as well as defective cell motility in response to PDGF, lamellipodium formation and Rac-mediated actin polymerization. These results imply a non-redundant role for WAVE2 in murine embryogenesis and a critical role for WAVE2 in actin-based processes downstream of Rac that are essential for cell movement.
Yan
Catherine
C
Center for Blood Research, 200 Longwood Avenue, Boston, MA 02115, USA.
Martinez-Quiles
Narcisa
N
Eden
Sharon
S
Shibata
Tomoyuki
T
Takeshima
Fuminao
F
Shinkura
Reiko
R
Fujiwara
Yuko
Y
Bronson
Roderick
R
Snapper
Scott B
SB
Kirschner
Marc W
MW
Geha
Raif
R
Rosen
Fred S
FS
Alt
Frederick W
FW
D000199:Actins / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001704:Biopolymers; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014923:Wiskott-Aldrich Syndrome / Q000097:blood / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D001704:Biopolymers; D008840:Microfilament Proteins; D020033:Protein Isoforms; D051300:Wiskott-Aldrich Syndrome Protein Family; D012313:RNA; D020744:rac GTP-Binding Proteins