Nadeau Valérie, Bissonauth Vickram, Charron Jean
Centre de recherche en cancérologie de l'université Laval, centre de recherche du centre hospitalier universitaire de Québec, Québec G1R 2J6, Canada.
Med Sci (Paris). 2012 Apr;28(4):409-15. doi: 10.1051/medsci/2012284019. Epub 2012 Apr 25.
The ERK/MAPK signaling pathway is involved in several cellular functions. Inactivation in mice of genes encoding members of this pathway is often associated with embryonic death resulting from abnormal placental development. The placenta is essential for nutritional and gaseous exchanges between maternal and embryonic circulations, as well as for the removal of metabolic wastes. These exchanges take place without direct contact between the two circulations. In mice, the hematoplacental barrier consists in a triple layer of trophoblast cells and endothelial cells of the embryo. MEK1 and MEK2 are double specificity serine-threonine/tyrosine kinases responsible for the activation of ERK1 and ERK2. Mek1 inactivation results in placental anomalies due to trophoblast cell proliferation and differentiation defects leading to severe delays in the development of placenta and causing the death of the embryo. Although Mek2(-/-) mutant mice survived without any apparent phenotype, double heterozygous Mek1(+/-)Mek2(+/-) mutants die during gestation from placental malformations. Together, these data emphasize the crucial role of the ERK/MAPK cascade in the formation of extraembryonic structures.
ERK/MAPK信号通路参与多种细胞功能。该信号通路成员编码基因在小鼠中的失活通常与胎盘发育异常导致的胚胎死亡有关。胎盘对于母体和胚胎循环之间的营养和气体交换以及代谢废物的清除至关重要。这些交换在两种循环不直接接触的情况下发生。在小鼠中，血胎盘屏障由胚胎的三层滋养层细胞和内皮细胞组成。MEK1和MEK2是双特异性丝氨酸 - 苏氨酸/酪氨酸激酶，负责激活ERK1和ERK2。Mek1失活会导致胎盘异常，这是由于滋养层细胞增殖和分化缺陷导致胎盘发育严重延迟并致使胚胎死亡。尽管Mek2(-/-)突变小鼠存活下来且没有任何明显表型，但双杂合子Mek1(+/-)Mek2(+/-)突变体在妊娠期间因胎盘畸形而死亡。总之，这些数据强调了ERK/MAPK级联在胚外结构形成中的关键作用。
