Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm
Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm
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DOI：
10.1101/gad.904601
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发表时间：
2001-08-01
影响因子：
10.5
通讯作者：
Zaret, KS
中科院分区：
文献类型：
--
作者：
Rossi, JM;Dunn, NR;Zaret, KS
中胚层信号对于胚胎内胚层分化为不同的组织域是至关重要的。鸡的经典组织移植实验和小鼠的最新研究表明，与心源性中胚层的相互作用是诱导肝脏进入前肠腹侧内胚层的必要条件和充分条件。利用分子标记和功能分析，我们现在发现横隔间充质细胞是一种独特的中胚层细胞类型，它与腹侧内胚层紧密相对，有助于肝脏的诱导。具体地说，使用小鼠Bmp4零突变和BMPs的抑制剂，我们发现来自横隔间充质的BMP信号对于诱导内胚层中的肝脏基因和排除胰腺命运是必要的。BMPS显然部分地通过影响GATA4转录因子的水平发挥作用，并且与来自心脏中胚层的成纤维细胞生长因子信号平行工作。BMP信号似乎对肝脏内胚层向肝芽的形态发生生长也至关重要。因此，肝脏的内胚层结构域是由来自不同中胚层来源的同时信号指定的。
Mesodermal signaling is critical for patterning the embryonic endoderm into different tissue domains. Classical tissue transplant experiments in the chick and recent studies in the mouse indicated that interactions with the cardiogenic mesoderm are necessary and sufficient to induce the liver in the ventral foregut endoderm. Using molecular markers and functional assays, we now show that septum transversum mesenchyme cells, a distinct mesoderm cell type, are closely apposed to the ventral endoderm and contribute to hepatic induction. Specifically, using a mouse Bmp4 null mutation and an inhibitor of BMPs, we find that BMP signaling from the septum transversum mesenchyme is necessary to induce liver genes in the endoderm and to exclude a pancreatic fate. BMPs apparently function, in part, by affecting the levels of the GATA4 transcription factor, and work in parallel to FGF signaling from the cardiac mesoderm. BMP signaling also appears critical for morphogenetic growth of the hepatic endoderm into a liver bud. Thus, the endodermal domain for the liver is specified by simultaneous signaling from distinct mesodermal sources.