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Prostaglandin E2 regulates liver versus pancreas cell-fate decisions and endodermal outgrowth

机译:前列腺素E2调节肝脏和胰腺细胞命运的决定以及内胚层的生长

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摘要

The liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here we describe prostaglandin E2 (PGE2) as a regulator of endodermal fate specification during development. Modulating PGE2 activity has opposing effects on liver versus pancreas specification in zebrafish embryos as wellas mouse endodermal progenitors. The PGE2 synthetic enzyme cox2a and receptor ep2a are patterned such that cells closest to PGE2 synthesis acquire a liver fate, whereas more distant cells acquire a pancreas fate. PGE2 interacts with the bmp2b pathway to regulate fate specification. At later stages of development, PGE2 acting via the ep4a receptor promotes outgrowth of both the liver and pancreas. PGE2 remains important for adult organ growth, as it modulates liver regeneration. This work provides invivo evidence that PGE2 mayact as a morphogen to regulate cell-fate decisions and outgrowth of the embryonic endodermal anlagen.
机译:肝脏和胰腺来自常见的内胚层祖细胞。如何指定这些不同的细胞命运知之甚少。在这里,我们将前列腺素E2(PGE2)描述为内胚乳命运规范的调节剂。在斑马鱼胚胎以及小鼠内胚层祖细胞中,调节PGE2活性对肝脏和胰脏指标具有相反的影响。对PGE2合成酶cox2a和受体ep2a进行构图,以便最接近PGE2合成的细胞获得肝脏命运,而更远的细胞获得胰腺命运。 PGE2与bmp2b途径相互作用以调节命运规范。在发育的后期,通过ep4a受体起作用的PGE2促进肝脏和胰腺的生长。 PGE2调节肝脏再生,因此对于成人器官的生长仍然很重要。这项工作提供了体内证据,证明PGE2可以作为形态发生因子来调节细胞命运决定和胚胎内胚层胶原蛋白的生长。

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