Heparan Sulfate Proteoglycans Regulate Fgf Signaling and Cell Polarity during Collective Cell Migration.
Heparan Sulfate Proteoglycans Regulate Fgf Signaling and Cell Polarity during Collective Cell Migration.
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DOI：
10.1016/j.celrep.2014.12.043
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发表时间：
2015-01-20
期刊：
影响因子：
8.8
通讯作者：
Piotrowski T
中科院分区：
文献类型：
--
作者：
Venero Galanternik M;Kramer KL;Piotrowski T
集体细胞迁移是胚胎发育和癌症侵袭期间高度调节的形态发生运动，涉及细胞自主机制和环境信号的精确编排和整合。协调的侧线原基迁移由趋化因子受体通过区室化Wnt/β-连环蛋白和Fgf信号传导的调节来控制。两个外生骨藻素糖基转移酶基因（extl 3，ext 2）的突变分析表明，硫酸乙酰肝素链的损失导致集体细胞迁移的失败，由于增强的FGF配体扩散和FGF信号转导的损失。因此，Wnt/β-连环蛋白信号传导被异位激活，导致随后的趋化因子受体cxcr 7 b的丧失。HSPG功能的破坏诱导广泛的，随机的丝状伪足形成，表明HSPG参与维持集体迁移细胞的细胞极性。HSPG本身受Wnt/β-连环蛋白和Fgf途径调节，因此是协调集体细胞迁移与器官特化和形态发生的调节网络的组成部分。
Collective cell migration is a highly regulated morphogenetic movement during embryonic development and cancer invasion that involves precise orchestration and integration of cell autonomous mechanisms and environmental signals. Coordinated lateral line primordium migration is controlled by the regulation of chemokine receptors via compartmentalized Wnt/β-catenin and Fgf signaling. Analysis of mutations in two exostosin glycosyltransferase genes (extl3, ext2) revealed that loss of Heparan Sulfate chains results in a failure of collective cell migration due to enhanced Fgf ligand diffusion and loss of Fgf signal transduction. Consequently, Wnt/β-catenin signaling is activated ectopically resulting in the subsequent loss of the chemokine receptor cxcr7b. Disruption of HSPG function induces extensive, random filopodia formation, demonstrating that HSPGs are involved in maintaining cell polarity in collectively migrating cells. HSPGs themselves are regulated by the Wnt/β-catenin and Fgf pathways and are therefore integral components of the regulatory network coordinating collective cell migration with organ specification and morphogenesis.