Centro Andaluz de Biología Molecular y Medicina Regenerativa-CIBERDEM, Sevilla, Spain.
Dev Biol. 2010 Oct 15;346(2):346-55. doi: 10.1016/j.ydbio.2010.07.032. Epub 2010 Aug 6.
The embryonic endoderm is a multipotent progenitor cell population that gives rise to the epithelia of the digestive and respiratory tracts, the liver and the pancreas. Among the transcription factors that have been shown to be important for endoderm development and gut morphogenesis is GATA4. Despite the important role of GATA4 in endoderm development, its transcriptional regulation is not well understood. In this study, we identified an intronic enhancer from the mouse Gata4 gene that directs expression to the definitive endoderm in the early embryo. The activity of this enhancer is initially broad in all endodermal progenitors, as demonstrated by fate mapping analysis using the Cre/loxP system, but becomes restricted to the dorsal foregut and midgut, and associated organs such as dorsal pancreas and stomach. The function of the intronic Gata4 enhancer is dependent upon a conserved Forkhead transcription factor-binding site, which is bound by recombinant FoxA2 in vitro. These studies identify Gata4 as a direct transcriptional target of FoxA2 in the hierarchy of the transcriptional regulatory network that controls the development of the definitive endoderm.
胚胎内胚层是一种多能祖细胞群体，它产生消化和呼吸道、肝脏和胰腺的上皮细胞。已经证明，在对内胚层发育和肠道形态发生很重要的转录因子中，有 GATA4。尽管 GATA4 在内胚层发育中起着重要作用，但它的转录调控还不是很清楚。在这项研究中，我们从鼠 Gata4 基因中鉴定出一个内含子增强子，该增强子在早期胚胎中指导向确定性内胚层表达。通过使用 Cre/loxP 系统的命运映射分析，证明该增强子的活性最初在所有内胚层祖细胞中广泛存在，但仅限于背侧前肠和中肠，以及相关器官，如背侧胰腺和胃。内含子 Gata4 增强子的功能依赖于一个保守的叉头转录因子结合位点，该位点在体外被重组 FoxA2 结合。这些研究表明，Gata4 是控制确定性内胚层发育的转录调控网络中 FoxA2 的直接转录靶标。
