Nijmeijer Rian M, Leeuwis Jan Willem, DeLisio Anna, Mummery Christine L, Chuva de Sousa Lopes Susana M
Hubrecht Institute, Netherlands Institute for Developmental Biology Utrecht, Uppsalalaan 8, 2584 CT Utrecht, The Netherlands.
Stem Cell Res. 2009 Sep-Nov;3(2-3):170-8. doi: 10.1016/j.scr.2009.06.003. Epub 2009 Jul 1.
The endoderm plays an inductive role in the formation of cardiomyocytes in many vertebrates. Here, we provide further evidence for this in the mouse and demonstrate enhanced cardiomyogenesis in mouse embryonic stem cells cultured in the presence of native visceral endoderm. Isolated mesoderm from late-primitive streak stage mouse embryos that still have an open proamniotic canal had a reduced capacity to form cardiomyocytes after 4 days in culture compared with mesoderm isolated from later stages but prior to cardiomyogenesis. Moreover, removal of the visceral endoderm but not the primitive streak reduced the formation of beating areas in embryo explants in culture. Coculture with the END2 cell line, which has visceral endoderm-like properties, restored the formation of beating areas. Immunohistochemical analysis showed that the expected candidate signaling pathways downstream of Wnts and bone morphogenetic proteins (BMPs) were active in the embryo at the appropriate time and place to be involved. Overall, the results show that, as in other vertebrates, the (visceral) endoderm plays an important role in the early events of mouse cardiomyogenesis.
在内胚层在许多脊椎动物心肌细胞形成过程中发挥诱导作用。在此，我们在小鼠中为此提供了进一步的证据，并证明在存在天然内脏内胚层的情况下培养的小鼠胚胎干细胞中，心肌生成增强。与从后期但在心肌生成之前分离的中胚层相比，从仍有开放羊膜管的晚期原条阶段小鼠胚胎中分离的中胚层在培养4天后形成心肌细胞的能力降低。此外，去除内脏内胚层而非原条会减少培养的胚胎外植体中跳动区域的形成。与具有内脏内胚层样特性的END2细胞系共培养可恢复跳动区域的形成。免疫组织化学分析表明，Wnt和骨形态发生蛋白（BMP）下游预期的候选信号通路在胚胎中在适当的时间和地点处于活跃状态，从而参与其中。总体而言，结果表明，与其他脊椎动物一样，（内脏）内胚层在小鼠心肌生成的早期事件中起重要作用。
