S1P-Yap1 Signaling Regulates Endoderm Formation Required for Cardiac Precursor Cell Migration in Zebrafish
S1P-Yap1 Signaling Regulates Endoderm Formation Required for Cardiac Precursor Cell Migration in Zebrafish
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DOI：
10.1016/j.devcel.2014.08.014
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发表时间：
2014-10-13
影响因子：
11.8
通讯作者：
Mochizuki, Naoki
中科院分区：
文献类型：
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作者：
Fukui, Hajime;Terai, Kenta;Mochizuki, Naoki
为了形成斑马鱼的原代心管，双侧心脏前体细胞（CPCs）向内胚层下的中线迁移。缺乏内胚层的突变体和有缺陷的鞘磷脂1-磷酸（Si P）信号的鱼表现为贲门裂。内胚层缺陷导致CPCs缺乏立足点，而sip信号突变体导致心裂的原因尚不清楚。本研究表明，Si - P信号通过yes相关蛋白1 （Yap1）依赖的内胚层存活调节CPC迁移。在spns2 （Si P转运体）和s1pr2 （S1P受体-2）突变体中发现的裂门可以通过yap1核定位形式的内胚层表达来挽救。yap1缺失使yap1 /Tead靶结缔组织生长因子a （Ctgfa）表达降低，从而增加内胚层细胞凋亡。ctgfa异型体同样表现出内胚层缺损和贲门裂。总的来说，我们发现S1pr2/ yap1调节的ctgfa表达对于CPC迁移所需的适当内胚层形成至关重要。
To form the primary heart tube in zebrafish, bilateral cardiac precursor cells (CPCs) migrate toward the midline beneath the endoderm. Mutants lacking endoderm and fish with defective sphingosine 1-phosphate (Si P) signaling exhibit cardia bifida. Endoderm defects lead to the lack of foothold for the CPCs, whereas the cause of cardia bifida in Si P signaling mutants remains unclear. Here we show that Si P signaling regulates CPC migration through Yes-associated protein 1 (Yap1)-dependent endoderm survival. Cardia bifida seen in spns2 (Si P transporter) morphants and s1pr2 (S1P receptor-2) morphants could be rescued by endodermal expression of nuclear localized form of yap1. yap1 nnorphants had decreased expression of the Yap1/Tead target connective tissue growth factor a (Ctgfa) and consequently increased endodermal cell apoptosis. Consistently, ctgfa morphants showed defects of the endodermal sheet and cardia bifida. Collectively, we show that S1pr2/Yap1-regulated ctgfa expression is essential for the proper endoderm formation required for CPC migration.