Signaling pathways controlling primordial germ cell migration in zebrafish
Signaling pathways controlling primordial germ cell migration in zebrafish
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DOI：
10.1242/jcs.01362
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发表时间：
2004-09-15
影响因子：
4
通讯作者：
Raz, E
中科院分区：
文献类型：
--
作者：
Dumstrei, K;Mennecke, R;Raz, E
在斑马鱼迁移过程中，原始生殖细胞（PGCs）依赖趋化因子SDF - 1a提供的方向线索，其受体为CXCR4b。CXCR4b激活在细胞内转化为定向迁移的分子机制尚不清楚。在此我们研究了两个重要的生化途径——依赖G蛋白和依赖磷脂酰肌醇3 -激酶（PI3K）的信号传导——在引导斑马鱼PGC迁移中的作用。我们发现Gi家族的G蛋白对定向迁移至关重要，但对PGC的运动性并非必需。抑制PGCs中的PI3K信号传导会减慢它们的迁移速度，并导致细胞形态异常以及丝状伪足稳定性降低。在定向PGC迁移过程中，PI3K活性产物——磷脂酰肌醇（3,4,5） - 三磷酸[PtdIns(3,4,5)P - 3]和/或磷脂酰肌醇（3,4） - 二磷酸[PtdIns(3,4)P - 2]的分布始终没有极化，并且降低这些3 - 磷酸肌醇的水平并不影响PGCs定向迁移的能力。因此我们得出结论，依赖Gi的信号传导对定向迁移至关重要，而PI3K途径对PGCs的实际运动性很重要。
During their migration, zebrafish primordial germ cells (PGCs) rely on directional cues provided by the chemokine SDF-1a, whose receptor is CXCR4b. The molecular mechanisms whereby CXCR4b activation is interpreted intracellularly into directional migration are not known. Here we investigate the role of two important biochemical pathways - G-protein-dependent and phosphoinositide 3-kinase (PI3K)-dependent signaling - in directing PGC migration in zebrafish. We show that G proteins of the Gi family are essential for directional migration but not for PGC motility. Inhibition of PI3K signaling in PGCs slows down their migration and leads to abnormal cell morphology as well as to reduced stability of filopodia. Invariably, during directed PGC migration, the distribution of the products of PI3K activity - phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P-3] and/or phosphatidylinositol (3,4)bisphosphate [PtdIns(3,4)P-2] - is not polarized, and reducing the level of these 3-phosphoinositides does not affect the ability of PGCs to migrate directionally. We therefore conclude that Gi-dependent signaling is essential for directional migration, whereas the PI3K pathway is important for the actual motility of PGCs.