Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation
Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation
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DOI：
10.1016/j.cell.2005.08.040
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发表时间：
2005-12-02
期刊：
影响因子：
64.5
通讯作者：
Rossant, J
中科院分区：
文献类型：
--
作者：
Niwa, H;Toyooka, T;Rossant, J
滋养外胚层（TE）是哺乳动物胚胎发生的第一个分化细胞系，形成胎盘，这是哺乳动物发育所特有的结构。TE的分化是哺乳动物早期发育的标志性事件，但这第一次分化事件的分子机制仍然不清楚。胚胎干（ES）细胞可以通过POU家族转录因子Oct 3/4的强制抑制诱导分化为TE谱系。我们在这里表明，这一事件可以通过Caudal相关同源异型框2（Cdx 2）的过表达来模拟，这足以产生适当的滋养层干细胞（T）细胞。Cdx 2参与Oct 3/4阻遏诱导的滋养外胚层分化，但对TS细胞自我更新至关重要。在植入前胚胎中，Cdx 2最初与Oct 3/4共表达，它们形成复合物，用于在ES细胞中相互抑制其靶基因。这表明，lineagspecific转录因子之间的相互抑制可能参与了哺乳动物发育的第一次分化事件。
Trophectoderm (TE), the first differentiated cell lineage of mammalian embryogenesis, forms the placenta, a structure unique to mammalian development. The differentiation of TE is a hallmark event in early mammalian development, but molecular mechanisms underlying this first differentiation event remain obscure. Embryonic stem (ES) cells can be induced to differentiate into the TE lineage by forced repression of the POU-family transcription factor, Oct3/4. We show here that this event can be mimicked by overexpression of Caudal-related homeobox 2 (Cdx2), which is sufficient to generate proper trophoblast stem (T) cells. Cdx2 is dispensable for trophectoderm differentiation induced by Oct3/4 repression but essential for TS cell self-renewal. In preimplantation embryos, Cdx2 is initially coexpressed with Oct3/4 and they form a complex for the reciprocal repression of their target genes in ES cells. This suggests that reciprocal inhibition between lineagespecific transcription factors might be involved in the first differentiation event of mammalian development.