Tead4 is required for specification of trophectoderm in pre-implantation mouse embryos
Tead4 is required for specification of trophectoderm in pre-implantation mouse embryos
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DOI：
10.1016/j.mod.2007.11.002
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发表时间：
2008-03-01
影响因子：
2.6
通讯作者：
Sasaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Nishioka, Noriyuki;Yamamoto, Shinji;Sasaki, Hiroshi
在植入前小鼠发育过程中，胚胎形成囊胚，并建立前两个细胞系：产生胎盘的滋养外胚层（TE）和将形成胚胎的内细胞团（ICM）。TE的分化受转录因子Caudal相关同源框2（Cdx 2）的调节，但Cdx 2表达上游的作用机制仍不清楚。在这里，我们表明，TEA结构域家族转录因子，Tead。4，是TE发展所必需的。Tead 1、Tead 2和Tead 4在植入前胚胎中表达，至少Tead 1和Tead 4在TE和ICM谱系中广泛表达。Tead 4（-/-）胚胎在着床前阶段死亡，没有形成囊胚腔。突变体胚胎继续细胞增殖，粘附连接和细胞极性没有显着影响。在Tead 4（-/-）胚胎中，Cdx 2在桑椹胚期弱表达，但在后期不表达。在Tead 4（-/-）胚胎中未检测到TE特异性基因，包括Eomes和Cdx 2独立基因Fgfr 2。相反，ICM特异性转录因子Oct 3/4和Nancy在所有卵裂球中表达。Tead 4（-/-）胚胎在体外培养时也不能分化为滋养层巨细胞。从Tead 4（-/-）胚胎中建立了具有正常体外分化能力的ES细胞。这些结果表明Tead 4在滋养外胚层中具有与Tead 1和Tead 2不同的作用。Tead 4是滋养外胚层谱系的特化和发育所需的早期转录因子，其包括Cdx 2的表达。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
During pre-implantation mouse development, embryos form blastocysts with establishment of the first two cell lineages: the trophectoderm (TE) which gives rise to the placenta, and the inner cell mass (ICM) which will form the embryo proper. Differentiation of TE is regulated by the transcription factor Caudal-related homeobox 2 (Cdx2), but the mechanisms which act upstream of Cdx2 expression remain unknown. Here we show that the TEA domain family transcription factor, Tead.4, is required for TE development. Tead1, Tead2 and Tead4 were expressed in pre-implantation embryos, and at least Tead1 and Tead4 were expressed widely in both TE and ICM lineages. Tead4(-/-) embryos died at pre-implantation stages without forming the blastocoel. The mutant embryos continued cell proliferation, and adherens junction and cell polarity were not significantly affected. In Tead4(-/-) embryos, Cdx2 was weakly expressed at the morula stage but was not expressed in later stages. None of the TE specific genes, including Eomes and a Cdx2 independent gene, Fgfr2, was detected in Tead4(-/-) embryos. Instead, the ICM specific transcription factors, Oct3/4 and Nancy, were expressed in all the blastomeres. Tead4(-/-) embryos also failed to differentiate trophoblast giant cells when they were cultured in vitro. ES cells with normal in vitro differentiation abilities were established from Tead4(-/-) embryos. These results suggest that Tead4 has a distinct role from Tead1 and Tead2 in trophectoderm. specification of preimplantation embryos, and that Tead4 is an early transcription factor required for specification and development of the trophectoderm lineage, which includes expression of Cdx2. (C) 2007 Elsevier Ireland Ltd. All rights reserved.