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

Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation
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DOI:
10.1101/gad.1022203
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发表时间:
2003-01-15
影响因子:
10.5
通讯作者:
He, X
He, X
中科院分区:
生物学1区
文献类型:
--
作者:
Habas, R;Dawid, IB;He, X

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Wnt/Frizzled(Fz)信号通过不完全定义的机制控制脊椎动物原肠胚形成期间的细胞极性/运动。我们以前证明,Wnt/Fz激活Rho,GT3和调节细胞骨架结构,是脊椎动物原肠胚形成所必需的。在这里,我们报告说,在哺乳动物细胞和非洲爪蟾胚胎,Wnt/Fz信号共激活Rho和Rac,另一个GTdR和不同的调节细胞骨架结构。Rac的Wnt/Fz激活独立于Rho,并介导Jun N末端激酶(JNK)的Wnt/Fz激活。Dishevelled(Dvl)是Fz下游的胞质蛋白,与Rac形成Wnt诱导的复合物,独立于Wnt诱导的Dv 1-Rho复合物。Rac功能的耗尽或抑制扰乱爪蟾原肠胚形成,而不影响Rho或β-连环蛋白途径的Wnt/Fz激活。我们建议,平行激活的Rac和Rho途径的Wnt/Fz信号是必需的细胞极性和运动在脊椎动物原肠胚形成。
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.