Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation

被引:461
作者
Habas, R
Dawid, IB
He, X [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp,Div Neurosci, Boston, MA 02115 USA
[2] NICHHD, Genet Mol Lab, Bethesda, MD 20892 USA
关键词
Wnt; Frizzled; Rac; Rho; gastrulation; vertebrates;
D O I
10.1101/gad.1022203
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Wnt/Frizzled (Fz) signaling controls cell polarity/movements during vertebrate gastrulation via incompletely defined mechanisms. We demonstrated previously that Wnt/Fz activation of Rho, a GTPase and regulator of cytoskeletal architecture, is essential for vertebrate gastrulation. Here we report that in mammalian cells and Xenopus embryos, Wnt/Fz signaling coactivates Rho and Rac, another GTPase and distinct regulator of cytoskeletal architecture. Wnt/Fz activation of Rac is independent of Rho and mediates Wnt/Fz activation of Jun N-terminal kinase (JNK). Dishevelled (Dvl), a cytoplasmic protein downstream of Fz, forms a Wnt-induced complex with Rac independent of the Wnt-induced Dv1-Rho complex. Depletion or inhibition of Rac function perturbs Xenopus gastrulation without affecting Wnt/Fz activation of the Rho or beta-catenin pathway. We propose that parallel activation of Rac and Rho pathways by Wnt/Fz signaling is required for cell polarity and movements during vertebrate gastrulation.
引用
收藏
页码:295 / 309
页数:15
相关论文
共 70 条
[1]   Planar signaling and morphogenesis in Drosophila [J].
Adler, PN .
DEVELOPMENTAL CELL, 2002, 2 (05) :525-535
[2]   Phosphoinositide 3-kinase-dependent and -independent activation of the small GTPase Rac2 in human neutrophils [J].
Akasaki, T ;
Koga, H ;
Sumimoto, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (25) :18055-18059
[3]  
Axelrod JD, 2001, GENE DEV, V15, P1182
[4]   Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways [J].
Axelrod, JD ;
Miller, JR ;
Shulman, JM ;
Moon, RT ;
Perrimon, N .
GENES & DEVELOPMENT, 1998, 12 (16) :2610-2622
[5]   Characterization of Rac and Cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases [J].
Benard, V ;
Bohl, BP ;
Bokoch, GM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (19) :13198-13204
[6]   Dishevelled: at the crossroads of divergent intracellular signaling pathways [J].
Boutros, M ;
Mlodzik, M .
MECHANISMS OF DEVELOPMENT, 1999, 83 (1-2) :27-37
[7]   Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling [J].
Boutros, M ;
Paricio, N ;
Strutt, DI ;
Mlodzik, M .
CELL, 1998, 94 (01) :109-118
[8]   A RETROVIRUS VECTOR EXPRESSING THE PUTATIVE MAMMARY ONCOGENE INT-1 CAUSES PARTIAL TRANSFORMATION OF A MAMMARY EPITHELIAL-CELL LINE [J].
BROWN, AMC ;
WILDIN, RS ;
PRENDERGAST, TJ ;
VARMUS, HE .
CELL, 1986, 46 (07) :1001-1009
[9]   Xenopus Cdc42 regulates convergent extension movements during gastrulation through Wnt/Ca2+ signaling pathway [J].
Choi, SC ;
Han, JK .
DEVELOPMENTAL BIOLOGY, 2002, 244 (02) :342-357
[10]   THE SMALL GTP-BINDING PROTEINS RAC1 AND CDC42 REGULATE THE ACTIVITY OF THE JNK/SAPK SIGNALING PATHWAY [J].
COSO, OA ;
CHIARIELLO, M ;
YU, JC ;
TERAMOTO, H ;
CRESPO, P ;
XU, NG ;
MIKI, T ;
GUTKIND, JS .
CELL, 1995, 81 (07) :1137-1146