Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
Dev Cell. 2014 Feb 24;28(4):423-37. doi: 10.1016/j.devcel.2014.01.006. Epub 2014 Feb 13.
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 well as 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 in vivo evidence that PGE2 may act as a morphogen to regulate cell-fate decisions and outgrowth of the embryonic endodermal anlagen.
肝脏和胰腺均起源于内胚层祖细胞。目前，人们对内胚层祖细胞特化成为不同细胞命运的分子机制知之甚少。本文描述了前列腺素 E2（PGE2）作为发育过程中内胚层命运特化的调节因子。在斑马鱼胚胎和小鼠内胚层祖细胞中，调节 PGE2 活性对肝脏与胰腺特化具有相反的影响。PGE2 合成酶 cox2a 和受体 ep2a 的表达模式是，离 PGE2 合成部位最近的细胞获得肝脏命运，而更远的细胞则获得胰腺命运。PGE2 通过与 bmp2b 信号通路相互作用来调节命运特化。在发育的后期阶段，PGE2 通过 ep4a 受体促进肝脏和胰腺的生长。PGE2 对于成体器官的生长也很重要，因为它可以调节肝脏再生。本研究提供了体内证据，表明 PGE2 可能作为一种形态发生素来调节细胞命运决定和胚胎内胚层原基的生长。
