Zebrafish Rho kinase 2 acts downstream of Wnt11 to mediate cell polarity and effective convergence and extension movements
Zebrafish Rho kinase 2 acts downstream of Wnt11 to mediate cell polarity and effective convergence and extension movements
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DOI：
10.1016/s0960-9822(02)00864-3
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发表时间：
2002-06-04
期刊：
影响因子：
9.2
通讯作者：
Solnica-Krezel, L
中科院分区：
文献类型：
--
作者：
Marlow, F;Topczewski, J;Solnica-Krezel, L
背景：脊椎动物原肠胚形成过程中，胚胎组织的收缩和伸展运动。在非洲爪蟾和斑马鱼中，非经典Wnt信号通路构成了与果蝇平面细胞极性通路对应的脊椎动物，并调节CE相关的中外侧细胞极化。尽管确定了正常CE所需的几种信号分子，但调节驱动CE的单个细胞行为的下游换能器才刚刚开始被阐明。此外，如何有缺陷的mediolateral细胞极性的影响CEis not understood.Results：在这里，我们表明，过度表达斑马鱼显性负性Rho激酶2（dnRok 2）破坏CE，而不改变细胞的命运，phenocopying非经典Wnt信号突变体。此外，Rho激酶2（Rok 2）过表达部分抑制slb/wnt 11原肠胚形成表型，和异位表达的非经典的p53调节Rok 2细胞内分布。此外，延时分析将有缺陷的背侧会聚运动与受损的细胞伸长、中外侧定向以及因此不能沿沿着直线路径迁移相关联。移植实验表明，野生型宿主中的dnRok 2细胞既不伸长也不定向它们的轴。与此相反，野生型细胞能够延长他们的细胞体在dnRok 2主机，即使他们无法定向axis.Conclusions：在斑马鱼原肠胚形成，Rok 2行为下游的非经典Wnt 11信号介导mediolateral细胞伸长所需的背细胞运动沿着直线路径。此外，细胞体的伸长和取向是需要细胞自主和非自主Rok 2功能的独立性质。
Background: During vertebrate gastrulation convergence and extension (CE), movements narrow and lengthen embryonic tissues. In Xenopus and zebrafish, a noncanonical Wnt signaling pathway constitutes the vertebrate counterpart to the Drosophila planar cell polarity pathway and regulates mediolateral cell polarization underlying CE. Despite the identification of several signaling molecules required for normal CE, the downstream transducers regulating individual cell behaviors driving CE are only beginning to be elucidated. Moreover, how defective mediolateral cell polarity impacts CE is not understood.Results: Here, we show that overexpression of zebrafish dominant-negative Rho kinase 2 (dnRok2) disrupts CE without altering cell fates, phenocopying noncanonical Wnt signaling mutants. Moreover, Rho kinase 2 (Rok2) overexpression partially suppresses the slb/wnt11 gastrulation phenotype, and ectopic expression of noncanonical Writs modulates Rok2 intracellular distribution. In addition, time-lapse analyses associate defective dorsal convergence movements with impaired cell elongation, mediolateral orientation, and consequently failure to migrate along straight paths. Transplantation experiments reveal that dnRok2 cells in wildtype hosts neither elongate nor orient their axes. In contrast, wild-type cells are able to elongate their cell bodies in dnRok2 hosts, even though they fail to orient their axes.Conclusions: During zebrafish gastrulation, Rok2 acts downstream of noncanonical Wnt11 signaling to mediate mediolateral cell elongation required for dorsal cell movement along straight paths. Furthermore, elongation and orientation of the cell body are independent properties that require both cell-autonomous and non-autonomous Rok2 function.