Department of Cell Biology, University of Alabama at Birmingham, AL 35294, USA.
Dev Biol. 2012 Apr 1;364(1):42-55. doi: 10.1016/j.ydbio.2012.01.008. Epub 2012 Jan 18.
Coordinated cell movements are crucial for vertebrate gastrulation and are controlled by multiple signals. Although many factors are shown to mediate non-canonical Wnt pathways to regulate cell polarity and intercalation during gastrulation, signaling molecules acting in other pathways are less investigated and the connections between various signals and cytoskeleton are not well understood. In this study, we show that the cytoplasmic tyrosine kinase Arg modulates gastrulation movements through control of actin remodeling. Arg is expressed in the dorsal mesoderm at the onset of gastrulation, and both gain- and loss-of-function of Arg disrupted axial development in Xenopus embryos. Arg controlled migration of anterior mesendoderm, influenced cell decision on individual versus collective migration, and modulated spreading and protrusive activities of anterior mesendodermal cells. Arg also regulated convergent extension of the trunk mesoderm by influencing cell intercalation behaviors. Arg modulated actin organization to control dynamic F-actin distribution at the cell-cell contact or in membrane protrusions. The functions of Arg required an intact tyrosine kinase domain but not the actin-binding motifs in its carboxyl terminus. Arg acted downstream of receptor tyrosine kinases to regulate phosphorylation of endogenous CrkII and paxillin, adaptor proteins involved in activation of Rho family GTPases and actin reorganization. Our data demonstrate that Arg is a crucial cytoplasmic signaling molecule that controls dynamic actin remodeling and mesodermal cell behaviors during Xenopus gastrulation.
协调的细胞运动对于脊椎动物原肠胚形成至关重要，并且受到多种信号的控制。尽管许多因素被证明可以通过调节细胞极性和原肠胚形成期间的细胞内突来介导非经典 Wnt 途径，但在其他途径中起作用的信号分子研究较少，并且各种信号和细胞骨架之间的联系也不清楚。在这项研究中，我们表明细胞质酪氨酸激酶 Arg 通过控制肌动蛋白重塑来调节原肠胚形成运动。Arg 在原肠胚形成开始时在背侧中胚层中表达，Arg 的功能获得和功能丧失都破坏了 Xenopus 胚胎的轴向发育。Arg 控制前中胚层的迁移，影响细胞在个体迁移和集体迁移之间的决策，并调节前中胚层细胞的扩散和突起活动。Arg 还通过影响细胞内突行为来调节躯干中胚层的会聚延伸。Arg 通过控制细胞-细胞接触处或膜突处的动态 F-肌动蛋白分布来调节肌动蛋白组织。Arg 的功能需要完整的酪氨酸激酶结构域，但不需要其羧基末端的肌动蛋白结合基序。Arg 作用于受体酪氨酸激酶下游，以调节内源性 CrkII 和桩蛋白的磷酸化，CrkII 和桩蛋白是参与 Rho 家族 GTP 酶激活和肌动蛋白重排的衔接蛋白。我们的数据表明，Arg 是一种关键的细胞质信号分子，可在 Xenopus 原肠胚形成过程中控制动态肌动蛋白重塑和中胚层细胞行为。
