Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein-coupled EP4 receptor during vertebrate gastrulation
Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein-coupled EP4 receptor during vertebrate gastrulation
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DOI：
10.1101/gad.1374506
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发表时间：
2006-01-01
影响因子：
10.5
通讯作者：
DuBois, RN
中科院分区：
文献类型：
--
作者：
Cha, YI;Kim, SH;DuBois, RN
原肠胚形成是胚胎发生过程中的一个基本过程，它通过细胞增殖、命运特化和运动的协同细胞活动塑造了恰当的身体结构并建立了三个胚层。尽管在脊椎动物原肠胚形成过程中，许多参与细胞命运特化和极性的分子途径已被确定，但对于赋予细胞运动性的信号传导却知之甚少。在此我们表明，微粒体前列腺素E - 2合酶（Ptges）产生的前列腺素E - 2（PGE(2)）对斑马鱼的原肠胚运动至关重要。此外，PGE(2)信号通过磷脂酰肌醇3 - 激酶（PI3K）/Akt，经由G蛋白偶联的PGE(2)受体（EP4）调节汇聚和延伸以及外包等形态发生运动。EP4信号对于恰当的细胞形状或迁移的持续性不是必需的，但它在原肠胚形成过程中促进了最佳的细胞迁移速度。这项工作证明了PGE(2)信号通过COX - 1 - Ptges - EP4途径促进细胞运动的关键需求，这是这种具有生物活性的脂质在动物早期发育中先前未被认识到的作用。
Gastrulation is a fundamental process during embryogenesis that shapes proper body architecture and establishes three germ layers through coordinated cellular actions of proliferation, fate specification, and movement. Although many molecular pathways involved in the specification of cell fate and polarity during vertebrate gastrulation have been identified, little is known of the signaling that imparts cell motility. Here we show that prostaglandin E-2 (PGE(2)) production by microsomal PGE(2) synthase (Ptges) is essential for gastrulation movements in zebrafish. Furthermore, PGE(2) signaling regulates morphogenetic movements of convergence and extension as well as epiboly through the G-protein-coupled PGE(2) receptor (EP4) via phosphatidylinositol 3-kinase (PI3K)/Akt. EP4 signaling is not required for proper cell shape or persistence of migration, but rather it promotes optimal cell migration speed during gastrulation. This work demonstrates a critical requirement of PGE(2) signaling in promoting cell motility through the COX-1-Ptaes-EP4 pathway, a previously unrecognized role for this biologically active lipid in early animal development.