Sritanaudomchai Hathaitip, Sparman Michelle, Tachibana Masahito, Clepper Lisa, Woodward Joy, Gokhale Sumita, Wolf Don, Hennebold Jon, Hurlbut William, Grompe Markus, Mitalipov Shoukhrat
Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
Dev Biol. 2009 Nov 1;335(1):179-87. doi: 10.1016/j.ydbio.2009.08.025. Epub 2009 Sep 3.
The first lineage decision during mammalian development is the establishment of the trophectoderm (TE) and the inner cell mass (ICM). The caudal-type homeodomain protein Cdx2 is implicated in the formation and maintenance of the TE in the mouse. However, the role of CDX2 during early embryonic development in primates is unknown. Here, we demonstrated that CDX2 mRNA levels were detectable in rhesus monkey oocytes, significantly upregulated in pronuclear stage zygotes, diminished in early cleaving embryos but restored again in compact morula and blastocyst stages. CDX2 protein was localized to the nucleus of TE cells but absent altogether in the ICM. Knockdown of CDX2 in monkey oocytes resulted in formation of early blastocyst-like embryos that failed to expand and ceased development. However, the ICM lineage of CDX2-deficient embryos supported the isolation of functional embryonic stem cells. These results provide evidence that CDX2 plays an essential role in functional TE formation during primate embryonic development.
哺乳动物发育过程中的第一个谱系决定是滋养外胚层(TE)和内细胞团(ICM)的形成。尾型同源域蛋白Cdx2与小鼠TE的形成和维持有关。然而,CDX2在灵长类动物早期胚胎发育中的作用尚不清楚。在此,我们证明恒河猴卵母细胞中可检测到CDX2 mRNA水平,在原核期受精卵中显著上调,在早期分裂胚胎中减少,但在致密桑椹胚和囊胚期再次恢复。CDX2蛋白定位于TE细胞的细胞核,但在ICM中完全不存在。在猴卵母细胞中敲低CDX2会导致形成早期囊胚样胚胎,这些胚胎无法扩张并停止发育。然而,CDX2缺陷胚胎的ICM谱系支持了功能性胚胎干细胞的分离。这些结果提供了证据,表明CDX2在灵长类动物胚胎发育过程中功能性TE的形成中起重要作用。