WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility

Catherine Yan; Narcisa Martinez-Quiles; Sharon Eden; Tomoyuki Shibata; Fuminao Takeshima; Reiko Shinkura; Yuko Fujiwara; Roderick Bronson; Scott B. Snapper; Marc W. Kirschner; Raif Geha; Fred S. Rosen; Frederick W. Alt

doi:10.1093/emboj/cdg350

WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility

Catherine Yan, Narcisa Martinez-Quiles, Sharon Eden, Tomoyuki Shibata, Fuminao Takeshima, Reiko Shinkura, Yuko Fujiwara, Roderick Bronson, Scott B. Snapper, Marc W. Kirschner, Raif Geha, Fred S. Rosen, Frederick W. Alt^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

155 Scopus citations

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.

Original language	English
Pages (from-to)	3602-3612
Number of pages	11
Journal	EMBO Journal
Volume	22
Issue number	14
DOIs	https://doi.org/10.1093/emboj/cdg350
State	Published - 15 Jul 2003
Externally published	Yes

Keywords

Actin polymerization
Lamellipodium
Rho GTPase
WASP-related protein
WAVE

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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.",

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author = "Catherine Yan and Narcisa Martinez-Quiles and Sharon Eden and Tomoyuki Shibata and Fuminao Takeshima and Reiko Shinkura and Yuko Fujiwara and Roderick Bronson and Snapper, {Scott B.} and Kirschner, {Marc W.} and Raif Geha and Rosen, {Fred S.} and Alt, {Frederick W.}",

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doi = "10.1093/emboj/cdg350",

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AU - Eden, Sharon

AU - Shibata, Tomoyuki

AU - Takeshima, Fuminao

AU - Shinkura, Reiko

AU - Fujiwara, Yuko

AU - Bronson, Roderick

AU - Snapper, Scott B.

AU - Kirschner, Marc W.

AU - Geha, Raif

AU - Rosen, Fred S.

AU - Alt, Frederick W.

PY - 2003/7/15

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N2 - 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.

AB - 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.

KW - Actin polymerization

KW - Lamellipodium

KW - Rho GTPase

KW - WASP-related protein

KW - WAVE

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WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility

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Keywords

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