Spagnoli Francesca M, Brivanlou Ali H
Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, NY 10021, USA.
Development. 2008 Feb;135(3):451-61. doi: 10.1242/dev.008458. Epub 2007 Dec 19.
Mechanisms underlying regional specification of distinct organ precursors within the endoderm, including the liver and pancreas, are still poorly understood. This is particularly true for stages between endoderm formation and the initiation of organogenesis. In this report, we have investigated these intermediate steps downstream of the early endodermal factor Gata5, which progressively lead to the induction of pancreatic fate. We have identified TGIF2 as a novel Gata5 target and demonstrate its function in the establishment of the pancreatic region within dorsal endoderm in Xenopus. TGIF2 acts primarily by restricting BMP signaling in the endoderm to allow pancreatic formation. Consistently, we found that blocking BMP signaling by independent means also perturbs the establishment of pancreatic identity in the endoderm. Previous findings demonstrated a crucial role for BMP signaling in determining dorsal/ventral fates in ectoderm and mesoderm. Our results now extend this trend to the endoderm and identify TGIF2 as the molecular link between dorsoventral patterning of the endoderm and pancreatic specification.
内胚层中不同器官前体（包括肝脏和胰腺）区域特化的潜在机制仍知之甚少。在内胚层形成和器官发生起始之间的阶段尤其如此。在本报告中，我们研究了早期内胚层因子Gata5下游的这些中间步骤，这些步骤逐步导致胰腺命运的诱导。我们已将TGIF2鉴定为一种新的Gata5靶标，并证明了其在非洲爪蟾背侧内胚层胰腺区域建立中的作用。TGIF2主要通过限制内胚层中的BMP信号传导来促进胰腺形成。同样，我们发现通过独立方法阻断BMP信号传导也会扰乱内胚层中胰腺特性的建立。先前的研究结果表明BMP信号传导在确定外胚层和中胚层的背/腹命运中起关键作用。我们现在的结果将这一趋势扩展到内胚层，并确定TGIF2是内胚层背腹模式与胰腺特化之间的分子联系。
