SERCA directs cell migration and branching across species and germ layers.

SERCA directs cell migration and branching across species and germ layers.
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DOI:
10.1242/bio.026039
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发表时间:
2017-10-15
期刊:
影响因子:
2.4
通讯作者:
Jesudason EC
Jesudason EC
中科院分区:
生物学4区
文献类型:
--
作者:
Bower DV;Lansdale N;Navarro S;Truong TV;Bower DJ;Featherstone NC;Connell MG;Al Alam D;Frey MR;Trinh LA;Fernandez GE;Warburton D;Fraser SE;Bennett D;Jesudason EC

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分支形态发生是脊椎动物和无脊椎动物器官发生的基础,但尚未完全了解。在这里,我们表明,肌质内质网钙再摄取泵(SERCA)指导芽跨越胚层和物种。克隆敲除证实了SERCA在果蝇气囊出芽中的细胞自主作用。果蝇气管发生的实时成像显示,迁移尖端细胞形成分支时Ca 2+水平升高。SERCA阻断取消了这种钙的差异,中止细胞迁移和新的分支。激活蛋白激酶C(PKC)拯救Ca2+在尖端细胞和恢复细胞迁移和分支。同样,抑制SERCA废除哺乳动物上皮出芽,PKC激活拯救出芽,而形态发生剂没有。中胚层(斑马鱼血管生成)和外胚层(果蝇神经系统)的行为相似,表明保守的要求细胞自主钙信号,建立SERCA,在迭代出芽。总结:活胚胎的动态成像表明,SERCA是一种保守的调节因子,控制细胞迁移和跨物种和胚层的分支,PKC激活可以挽救SERCA抑制。这篇文章有一个相关的第一人称采访的第一作者的文件作为补充信息的一部分。
Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca2+ reuptake pump (SERCA) directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in Drosophila air sac budding. Live imaging of Drosophila tracheogenesis revealed elevated Ca2+ levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca2+ differential, aborting both cell migration and new branching. Activating protein kinase C (PKC) rescued Ca2+ in tip cells and restored cell migration and branching. Likewise, inhibiting SERCA abolished mammalian epithelial budding, PKC activation rescued budding, while morphogens did not. Mesoderm (zebrafish angiogenesis) and ectoderm (Drosophila nervous system) behaved similarly, suggesting a conserved requirement for cell-autonomous Ca2+ signaling, established by SERCA, in iterative budding. Summary: Dynamic imaging of living embryos demonstrates that SERCA is a conserved regulator that controls cell migration and branching across species and germ layers, and PKC activation can rescue SERCA inhibition. This article has an associated First Person interview with the first author of the paper as part of the supplementary information.
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