title: WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility.
abstract: 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.
authors.affiliation: Center for Blood Research, 200 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Yan
authors.forename: Narcisa
authors.initials: N
authors.lastname: Martinez-Quiles
authors.forename: Sharon
authors.initials: S
authors.lastname: Eden
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Fuminao
authors.initials: F
authors.lastname: Takeshima
authors.forename: Reiko
authors.initials: R
authors.lastname: Shinkura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Roderick
authors.initials: R
authors.lastname: Bronson
authors.forename: Scott B
authors.initials: SB
authors.lastname: Snapper
authors.forename: Marc W
authors.initials: MW
authors.lastname: Kirschner
authors.forename: Raif
authors.initials: R
authors.lastname: Geha
authors.forename: Fred S
authors.initials: FS
authors.lastname: Rosen
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
mesh_terms: 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*
chemical_list: D000199:Actins; D001704:Biopolymers; D008840:Microfilament Proteins; D020033:Protein Isoforms; D051300:Wiskott-Aldrich Syndrome Protein Family; D012313:RNA; D020744:rac GTP-Binding Proteins