Essential requirement of CCAAT/enhancer binding proteins in embryogenesis
Essential requirement of CCAAT/enhancer binding proteins in embryogenesis
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DOI：
10.1128/mcb.24.22.9744-9751.2004
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发表时间：
2004-11-01
影响因子：
5.3
通讯作者：
Leutz, A
中科院分区：
文献类型：
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作者：
Bégay, V;Smink, J;Leutz, A
CCAAT/增强子结合蛋白C/EBPalpha和C/EBPbeta是相关的转录因子，对出生后小鼠的各种器官的功能很重要。基因置换和组织培养实验表明，这两个转录因子的部分冗余。在这里，我们表明，小鼠胚胎缺乏C/EBPalpha和C/EBPbeta（C/EBPalphabeta（-/-））死亡之间的胚胎第10天（E10）和E11和显示缺陷胎盘。原位杂交显示，C/EBPalpha和C/EBPbeta在E9.5的绒毛板中共表达，随后在绒毛膜层的滋养层中共表达。在C/EB Palphabeta（-/-）胎盘，尿囊血管侵入绒毛膜;然而，血管扩张和发育的绒毛膜层受损。此外，在不存在C/EBP β的情况下的C/EBP α或在不存在C/EBP α的情况下的C/EBP β的单个拷贝足以完成发育，这表明这些C/EBP在胚胎发生期间的互补。然而，在没有C/EBP β的情况下，C/EBP α的单拷贝未能挽救出生后的存活率，表明新生儿中C/EBP α的单倍不足。因此，我们的数据揭示了新的必要的，冗余的和剂量依赖性的功能的C/EBP。
The CCAAT/enhancer binding proteins C/EBPalpha and C/EBPbeta are related transcription factors that are important for the function of various organs in the postnatal mouse. Gene replacement and tissue culture experiments have suggested partial redundancy of both transcription factors. Here we show that mouse embryos deficient of both C/EBPalpha and C/EBPbeta (C/EBPalphabeta(-/-)) die between embryonic day 10 (E10) and E11 and display defective placentas. In situ hybridization revealed that C/EBPalpha and C/EBPbeta are coexpressed in the chorionic plate at E9.5 and later in the trophoblasts of the labyrinthine layer. In C/EBPalphabeta(-/-) placentas, allantoic blood vessels invaded the chorion; however, vessel expansion and development of the labyrinthine layer was impaired. Furthermore, a single copy of either C/EBPalpha in the absence of C/EBPbeta or C/EBPbeta in the absence of C/EBPalpha is sufficient to complete development, suggesting complementation of these C/EBPs during embryogenesis. A single copy of C/EBPalpha in the absence of C/EBPbeta, however, fails to rescue survival after birth, suggesting haploinsufficiency of C/EBPalpha in newborns. Our data thus reveal novel essential, redundant, and dosage dependent functions of C/EBPs.