Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa
Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa
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DOI：
10.1128/mcb.20.7.2466-2474.2000
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发表时间：
2000-04-01
影响因子：
5.3
通讯作者：
Wegner, M
中科院分区：
文献类型：
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作者：
Schreiber, J;Riethmacher-Sonnenberg, E;Wegner, M
GCM家族的转录因子包括果蝇GCM（果蝇中神经胶质生成的重要调节因子）及其两种哺乳动物同源物GCMa和GCMb。为了阐明这些哺乳动物同源物的功能，我们在小鼠中删除了GCMa。小鼠GCMa（mGCMa）的基因消除是胚胎致死的，小鼠在交配后9.5至10天死亡。在死亡时，胚胎本身没有明显的异常。神经系统发育，特别是，没有受到损害，因为可能已经预期在类似的果蝇GCM。相反，胎盘衰竭是死亡的原因。与胎盘滋养层中mGCMa的选择性表达一致，突变胎盘没有发育出功能性迷路层，这是母体和胎儿血液之间营养和气体交换所必需的。只有少数胎儿血管进入胎盘，不能正常生长和分支，胎盘滋养层细胞不能分化。胎盘的所有其他层，包括海绵滋养层和巨细胞层，正常形成。我们的结果表明，mGCMa在滋养层分化和胎盘正常血管化所需的信号转导过程中起着关键作用。
The GCM family of transcription factors consists of Drosophila melanogaster GCM, an important regulator of gliogenesis in the fly, and its two mammalian homologs, GCMa and GCMb. To clarify the function of these mammalian homologs, we deleted GCMa in mice. Genetic ablation of murine GCMa (mGCMa) is embryonic lethal, with mice dying between 9.5 and 10 days postcoitum. At the time of death, no abnormalities were apparent in the embryo proper. Nervous system development, in particular, was not impaired, as might have been expected in analogy to Drosophila GCM. Instead, placental failure was the cause of death. In agreement with the selective expression of mGCMa in labyrinthine trophoblasts, mutant placentas did not develop a functional labyrinth layer, which is necessary for nutrient and gas exchange between maternal and fetal blood. Only a few fetal blood vessels entered the placenta, and these failed to thrive and branch normally, Labyrinthine trophoblasts did not differentiate. All other layers of the placenta, including spongiotrophoblast and giant cell layer, formed normally, Our results indicate that mGCMa plays a critical role in trophoblast differentiation and the signal transduction processes required for normal vascularization of the placenta.