JunB is essential for mammalian placentation
JunB is essential for mammalian placentation
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DOI：
10.1093/emboj/18.4.934
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发表时间：
1999-02-15
期刊：
影响因子：
11.4
通讯作者：
Wagner, EF
中科院分区：
文献类型：
--
作者：
Schorpp-Kistner, M;Wang, ZQ;Wagner, EF
JunB是一种直接早期基因产物，也是AP-1转录因子家族的成员，缺乏JunB会导致E8.5和E10.0之间的胚胎死亡。虽然突变胚胎的生长发育严重迟缓，但细胞增殖显然没有受到损害。由于胚胎外组织中存在多种缺陷，导致junB缺陷胚胎无法与母体循环建立适当的血管相互作用，从而导致发育迟缓和胚胎死亡。这种表型缺陷的发生与野生型胚胎外组织中junB的高表达密切相关。在滋养细胞中，JunB的缺乏导致增殖素、基质金属蛋白酶-9 （MMP-9）和尿激酶纤溶酶原激活物（uPA）基因表达的失调，导致蜕膜新生血管的缺陷。由于vegf受体1 （flt-1）的下调，卵黄囊中胚层血管出现扩张。将junB（-/-）胚胎干细胞注射到四倍体野生型囊胚中可以部分恢复，胚胎不再发育迟缓，显示出正常的胎盘迷宫。因此，junB可能参与了多种信号通路的调节基因，这些基因参与了正常胎母循环系统的建立。
Lack of JunB, an immediate early gene product and member of the AP-1 transcription factor family causes embryonic lethality between E8.5 and E10.0. Although mutant embryos are severely retarded in growth and development, cellular proliferation is apparently not impaired. Retardation and embryonic death are caused by the inability of JunB-deficient embryos to establish proper vascular interactions with the maternal circulation due to multiple defects in extra-embryonic tissues, The onset of the phenotypic defects correlates well with high expression of junB in wild-type extra-embryonic tissues. In trophoblasts, the lack of JunB causes a deregulation of proliferin, matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA) gene expression, resulting in a defective neovascularization of the decidua, As a result of downregulation of the VEGF-receptor 1 (flt-1), blood vessels in the yolk sac mesoderm appeared dilated, Mutant embryos which escape these initial defects finally die from a nonvascularized placental labyrinth Injection of junB(-/-) embryonic stem (ES) cells into tetraploid wild-type blastocysts resulted in a partial rescue, in which the ES cell-derived fetuses were no longer growth retarded and displayed a normal placental labyrinth, Therefore, JunB appears to be involved in multiple signaling pathways regulating genes involved in the establishment of a proper fete-maternal circulatory system.