从非经典 Wnt 信号到经典 Wnt 信号的转变通过 Slt-Robo 和 RGA-9b/ARHGAP 依赖性机制停止神经母细胞迁移。
A switch from noncanonical to canonical Wnt signaling stops neuroblast migration through a Slt-Robo and RGA-9b/ARHGAP-dependent mechanism.
机构信息
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands;
出版信息
Proc Natl Acad Sci U S A. 2021 Mar 23;118(12). doi: 10.1073/pnas.2013239118.
Members of the Wnt family of secreted glycoproteins regulate cell migration through distinct canonical and noncanonical signaling pathways. Studies of vertebrate development and disease have shown that these pathways can have opposing effects on cell migration, but the mechanism of this functional interplay is not known. In the nematode , a switch from noncanonical to canonical Wnt signaling terminates the long-range migration of the QR neuroblast descendants, providing a tractable system to study this mechanism in vivo. Here, we show that noncanonical Wnt signaling acts through PIX-1/RhoGEF, while canonical signaling directly activates the Slt-Robo pathway component EVA-1/EVA1C and the Rho GTPase-activating protein RGA-9b/ARHGAP, which are required for migration inhibition. Our results support a model in which cross-talk between noncanonical and canonical Wnt signaling occurs through antagonistic regulation of the Rho GTPases that drive cell migration.
Wnt 家族的分泌糖蛋白成员通过不同的经典和非经典信号通路调节细胞迁移。脊椎动物发育和疾病的研究表明，这些通路可能对细胞迁移产生相反的影响，但这种功能相互作用的机制尚不清楚。在线虫中，从非经典 Wnt 信号到经典 Wnt 信号的转变终止了 QR 神经母细胞后代的长距离迁移，为在体内研究这种机制提供了一个可行的系统。在这里，我们表明非经典 Wnt 信号通过 PIX-1/RhoGEF 发挥作用，而经典信号直接激活 Slt-Robo 途径成分 EVA-1/EVA1C 和 Rho GTPase 激活蛋白 RGA-9b/ARHGAP，这对于迁移抑制是必需的。我们的结果支持这样一种模型，即非经典和经典 Wnt 信号之间的串扰通过对驱动细胞迁移的 Rho GTPases 的拮抗调节发生。
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