Deutsch G, Jung J, Zheng M, Lóra J, Zaret K S
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA.
Development. 2001 Mar;128(6):871-81. doi: 10.1242/dev.128.6.871.
The pancreas emerges independently from dorsal and ventral domains of embryonic gut endoderm. Gene inactivation experiments in mice have identified factors required for dorsal pancreas development, but factors that initiate the ventral pancreas have remained elusive. In this study, we investigated the hypothesis that the emergence of the ventral pancreas is related to the emergence of the liver. We find that the liver and ventral pancreas are specified at the same time and in the same general domain of cells. Using embryo tissue explantation experiments, we find that the default fate of the ventral foregut endoderm is to activate the pancreas gene program. FGF signalling from the cardiac mesoderm diverts this endoderm to express genes for liver instead of those for pancreas. No evidence was found to indicate that the cell type choice for pancreas or liver involves a selection for growth or viability. Cardiac mesoderm or FGF induces the local expression of sonic hedgehog, which in turn is inhibitory to pancreas but not to liver. The bipotential precursor cell population for pancreas and liver in embryonic development and its fate selection by FGF has features that appear to be recapitulated in the adult pancreas and are reflected in the evolution of these organs.
胰腺独立起源于胚胎肠道内胚层的背侧和腹侧区域。小鼠基因失活实验已确定了背侧胰腺发育所需的因子，但启动腹侧胰腺发育的因子仍不清楚。在本研究中，我们探讨了腹侧胰腺的出现与肝脏的出现相关这一假说。我们发现肝脏和腹侧胰腺是在同一时间、在相同的细胞总体区域中特化形成的。通过胚胎组织外植体实验，我们发现腹侧前肠内胚层的默认命运是激活胰腺基因程序。来自心脏中胚层的成纤维细胞生长因子（FGF）信号将该内胚层转向表达肝脏而非胰腺的基因。未发现有证据表明胰腺或肝脏的细胞类型选择涉及生长或生存能力的选择。心脏中胚层或FGF诱导音猬因子的局部表达，而音猬因子反过来对胰腺有抑制作用，但对肝脏没有抑制作用。胚胎发育中胰腺和肝脏的双潜能前体细胞群及其由FGF介导的命运选择具有一些特征，这些特征似乎在成体胰腺中得以重现，并反映在这些器官的进化过程中。
