Requirement for Map2k1 (Mek1) in extra-embryonic ectoderm during placentogenesis
Requirement for Map2k1 (Mek1) in extra-embryonic ectoderm during placentogenesis
复制标题
DOI：
10.1242/dev.02526
复制
发表时间：
2006-09-01
期刊：
影响因子：
4.6
通讯作者：
Charron, Jean
中科院分区：
文献类型：
--
作者：
Bissonauth, Vickram;Roy, Sophie;Charron, Jean
Map 2k 1（-/-）胚胎在妊娠中期死于异常发育和胎盘血管形成不足。我们现在发现，这种表型与迷路细胞增殖减少和细胞凋亡增加有关。尽管MAP 2K 1和MAP 2K 2的激活广泛存在于迷路区域，但MAPK 1和MAPK 3的激活仅限于母体鼻窦内衬的细胞，这表明ERK/MAPK级联反应在这些细胞中发挥重要作用。在Map 2k 1（-/-）胎盘中，ERK/MAPK级联激活受到干扰。在Map 2k 1（-/-）胎盘中也观察到合胞体滋养细胞的异常定位，即使该细胞谱系在胎盘发生期间的正确时间被指定。在四倍体实验中可以挽救胎盘表型。此外，胚胎中的Map 2k 1特异性缺失导致正常胚胎发育和存活的Map 2k 1（-/-）小鼠的出生。总之，这些数据启发Map 2k 1在胎盘发生过程中的胚外外胚层的重要作用。在胚胎中，Map 2k 1基因的功能似乎是不稳定的。
Map2k1(-/-) embryos die at mid-gestation from abnormal development and hypovascularization of the placenta. We now show that this phenotype is associated with a decreased labyrinth cell proliferation and an augmented cell apoptosis. Although the activation of MAP2K1 and MAP2K2 is widespread in the labyrinthine region, MAPK1 and MAPK3 activation is restricted to the cells lining the maternal sinuses, suggesting an important role for the ERK/MAPK cascade in these cells. In Map2k1(-/-) placenta, ERK/MAPK cascade activation is perturbed. Abnormal localization of the syncytiotrophoblasts is also observed in Map2k1(-/-) placenta, even though this cell lineage is specified at the correct time during placentogenesis. The placental phenotype can be rescued in tetraploid experiments. In addition, Map2k1-specific deletion in the embryo leads to normal embryo development and to the birth of viable Map2k1(-/-) mice. Altogether, these data enlighten the essential role of Map2k1 in extra-embryonic ectoderm during placentogenesis. In the embryo, the Map2k1 gene function appears dispensable.