Dynamic changes in Sox2 spatio-temporal expression promote the second cell fate decision through Fgf4/Fgfr2 signaling in preimplantation mouse embryos.
Dynamic changes in Sox2 spatio-temporal expression promote the second cell fate decision through Fgf4/Fgfr2 signaling in preimplantation mouse embryos.
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DOI：
10.1042/bcj20170418
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发表时间：
2018-03-20
期刊：
影响因子：
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通讯作者：
Robson P
中科院分区：
文献类型：
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作者：
Mistri TK;Arindrarto W;Ng WP;Wang C;Lim LH;Sun L;Chambers I;Wohland T;Robson P
Oct4和Sox2通过结合各自的调控基序来调控Nanog、Fgf4和Utf1等靶基因的表达。它们的功能合作反映在它们在相邻的顺式调控基序上异二聚化的能力，即复合的Sox/Oct基序。鉴于Oct4和Sox2调控许多发育基因，定量分析它们对不同Sox/Oct基序的协同作用将为早期胚胎发育的机制提供有价值的见解。在本研究中，我们使用荧光相关光谱测量了Oct4和Sox2对不同Sox/Oct基序的结合亲和力。我们发现，在Fgf4 Sox/Oct基序的情况下，协同结合相互作用主要由Sox2水平驱动。考虑到Sox2表达水平比Oct4波动更大，我们的发现为Sox2如何控制发育中的啮齿动物囊胚内细胞团内外胚层和原始内胚层群体的分离提供了解释。
Oct4 and Sox2 regulate the expression of target genes such as Nanog, Fgf4, and Utf1, by binding to their respective regulatory motifs. Their functional cooperation is reflected in their ability to heterodimerize on adjacent cis regulatory motifs, the composite Sox/Oct motif. Given that Oct4 and Sox2 regulate many developmental genes, a quantitative analysis of their synergistic action on different Sox/Oct motifs would yield valuable insights into the mechanisms of early embryonic development. In the present study, we measured binding affinities of Oct4 and Sox2 to different Sox/Oct motifs using fluorescence correlation spectroscopy. We found that the synergistic binding interaction is driven mainly by the level of Sox2 in the case of the Fgf4 Sox/Oct motif. Taking into account Sox2 expression levels fluctuate more than Oct4, our finding provides an explanation on how Sox2 controls the segregation of the epiblast and primitive endoderm populations within the inner cell mass of the developing rodent blastocyst.