Phosphoinositide 3-kinase is required for process outgrowth and cell polarization of gastrulating mesendodermal cells
Phosphoinositide 3-kinase is required for process outgrowth and cell polarization of gastrulating mesendodermal cells
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DOI：
10.1016/s0960-9822(03)00505-0
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发表时间：
2003-08-05
期刊：
影响因子：
9.2
通讯作者：
Heisenberg, CP
中科院分区：
文献类型：
--
作者：
Montero, JA;Kilian, B;Heisenberg, CP
背景资料：在脊椎动物原肠胚形成过程中，细胞极化和迁移是细胞重排的核心组成部分，导致外胚层、中胚层和内胚层三个胚层的形成。先前的研究表明Wnt/平面细胞极性（PCP）信号通路在原肠胚形成过程中控制细胞形态和运动。然而，细胞极化和定向细胞迁移减少，但没有完全取消在Wnt/PCP信号的情况下，这一观察表明，其他信号通路必须involved.Results：我们表明，磷酸肌醇3-激酶（PI 3 Ks）需要在发病的斑马鱼原肠胚在中内胚层细胞的过程形成和细胞极化。血小板衍生生长因子（PDGF）在PI 3 K的上游起作用，而蛋白激酶B（PK B）是PI 3 K活性的下游效应物，定位于迁移中内胚层细胞的前缘。在PI 3 K活性的情况下，PKB的本地化和细胞极化强烈减少中内胚层细胞，其次是缓慢的，但仍然高度协调和直接的运动这些cells.Conclusions：我们已经确定了一个新的作用的信号通路组成的PDGF，PI 3 K，和PKB在控制原肠胚形成过程中的形态发生细胞运动。此外，我们的研究结果提供了深入了解细胞极化和定向细胞迁移在斑马鱼原肠胚形成的发病之间的关系。
Background: During vertebrate gastrulation, cell polarization and migration are core components in the cellular rearrangements that lead to the formation of the three germ layers, ectoderm, mesoderm, and endoderm. Previous studies have implicated the Wnt/planar cell polarity (PCP) signaling pathway in controlling cell morphology and movement during gastrulation. However, cell polarization and directed cell migration are reduced but not completely abolished in the absence of Wnt/PCP signals; this observation indicates that other signaling pathways must be involved.Results: We show that Phosphoinositide 3-Kinases (PI3Ks) are required at the onset of zebrafish gastrulation in mesendodermal cells for process formation and cell polarization. Platelet Derived Growth Factor (PDGF) functions upstream of PI3K, while Protein Kinase B (PKB), a downstream effector of PI3K activity, localizes to the leading edge of migrating mesendodermal cells. In the absence of PI3K activity, PKB localization and cell polarization are strongly reduced in mesendodermal cells and are followed by slower but still highly coordinated and directed movements of these cells.Conclusions: We have identified a novel role of a signaling pathway comprised of PDGF, PI3K, and PKB in the control of morphogenetic cell movements during gastrulation. Furthermore, our findings provide insight into the relationship between cell polarization and directed cell migration at the onset of zebrafish gastrulation.