MicroRNA-206 Regulates Cell Movements during Zebrafish Gastrulation by Targeting prickle1a and Regulating c-Jun N-Terminal Kinase 2 Phosphorylation
MicroRNA-206 Regulates Cell Movements during Zebrafish Gastrulation by Targeting prickle1a and Regulating c-Jun N-Terminal Kinase 2 Phosphorylation
复制标题
MicroRNA-206 通过靶向 prickle1a 和调节 c-Jun N 末端激酶 2 磷酸化来调节斑马鱼原肠胚形成过程中的细胞运动
DOI：
10.1128/mcb.00134-12
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发表时间：
2012-07-01
影响因子：
5.3
通讯作者：
Wang, Qiang
中科院分区：
文献类型：
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作者：
Liu, Xiuli;Ning, Guozhu;Wang, Qiang
摘要在脊椎动物原肠发育过程中，轴的形成既需要同时发生的诱导事件，也需要细胞的运动。会聚和伸展(CE)运动有助于缩小和延长形成胚轴。MicroRNAs(MiRNAs)在调节细胞的基本功能和发育过程中起着关键作用，但其在CE运动中的作用尚不清楚。斑马鱼mir206是母性表达的，并存在于整个胚泡和原肠发育时期。Mir206功能的获得或丧失都会导致细胞自主和非细胞自主的会聚伸展运动的严重缺陷。马赛克谱系追踪研究表明，在mir206过表达的胚胎或mir206变异体中，膜突起和肌动蛋白细丝的形成受到干扰。在机制上，mir206靶向刺激素1a(Pk1a)mRNA，从而调节c-jun氨基末端蛋白激酶2(JNK2)的磷酸化。Pk1a过表达或敲除可分别挽救由mir206过表达或敲除引起的收敛延伸缺陷。因此，mir206通过调节丝裂原活化蛋白激酶(MAPK)JNK信号，对正常的会聚和伸展运动起着至关重要的调节作用。
ABSTRACT During vertebrate gastrulation, both concurrent inductive events and cell movements are required for axis formation. Convergence and extension (CE) movements contribute to narrowing and lengthening the forming embryonic axis. MicroRNAs (miRNAs) play a critical role in regulating fundamental cellular functions and developmental processes, but their functions in CE movements are not well known. Zebrafish mir206 is maternally expressed and present throughout blastulation and gastrulation periods. Either gain or loss of function of mir206 leads to severe defects of convergent extension movements both cell autonomously and non-cell autonomously. Mosaic lineage tracing studies reveal that the formation of membrane protrusions and actin filaments is disturbed in mir206-overexpressing embryos or mir206 morphants. Mechanistically, mir206 targets prickle1a (pk1a) mRNA and as a result regulates c-Jun N-terminal protein kinase 2 (JNK2) phosphorylation. pk1a overexpression or knockdown can rescue convergent extension defects induced by mir206 overexpression or knockdown, respectively. Therefore, mir206 is an essential, novel regulator for normal convergent and extension movements by regulating mitogen-activated protein kinase (MAPK) JNK signaling.