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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism*
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Actins / physiology
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Animals
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Biopolymers
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Cell Line
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Cell Movement / physiology*
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Cytoskeleton / metabolism
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Embryo, Mammalian / cytology
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Embryo, Mammalian / physiology*
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Gene Deletion
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Mice
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Mice, Knockout
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Microfilament Proteins / deficiency*
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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Mutation
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Protein Isoforms / deficiency
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Pseudopodia / metabolism
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RNA / metabolism
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Stem Cells / cytology
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Stem Cells / metabolism
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Wiskott-Aldrich Syndrome / blood
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Wiskott-Aldrich Syndrome / metabolism
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Wiskott-Aldrich Syndrome Protein Family
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rac GTP-Binding Proteins / metabolism*
Substances
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Actins
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Biopolymers
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Microfilament Proteins
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Protein Isoforms
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Wiskott-Aldrich Syndrome Protein Family
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RNA
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rac GTP-Binding Proteins