Abstract
Eras encodes a Ras-like GTPase protein that was originally identified as an embryonic stem cell-specific Ras. ERAS has been known to be required for the growth of embryonic stem cells and stimulates somatic cell reprogramming, suggesting its roles on mouse early embryonic development. We now report a dynamic expression pattern of Eras during mouse peri-implantation development: its expression increases at the blastocyst stage, and specifically decreases in E7.5 mesoderm. In accordance with its expression pattern, the increased expression of Eras promotes cell proliferation through controlling AKT activation and the commitment from ground to primed state through ERK activation in mouse embryonic stem cells; and the reduced expression of Eras facilitates primitive streak and mesoderm formation through AKT inhibition during gastrulation. The expression of Eras is finely regulated to match its roles in mouse early embryonic development during which Eras expression is negatively regulated by the β-catenin pathway. Thus, beyond its well-known role on cell proliferation, ERAS may also play important roles in cell lineage specification during mouse early embryonic development.
Highlights
Totipotent mammalian zygote undergoes several cleavage divisions to form the blastocyst composed of the trophoblast and inner cell mass which continuously segregates into the hypoblast and the epiblast [1]
Real-time RT-PCR showed that Eras mRNA was highly expressed in E5.5–7.5 endoderm and epiblast compared with its expression in E7.5 mesoderm
Eras was initially screened as a Ras family protein expressed in embryonic stem cells (ESCs), and its mutation does not lead to an obvious phenotype in mice [26]
Summary
Totipotent mammalian zygote undergoes several cleavage divisions to form the blastocyst composed of the trophoblast and inner cell mass which continuously segregates into the hypoblast and the epiblast [1]. Because the epiblast can give rise to all cell lineages of the fetus and individual epiblast cells can commit into three germ layers when they are injected into blastocyst, pre-implantation epiblast is thought to be the developmental ground state [2]. The embryo dramatically increases its cell number dependent on a rapid burst of pluripotent cell proliferation with average generation times of approximately 4.5–8.0 h [3]; at the same time, the embryo enters the primed state and initiates cell lineage specification through gastrulation, during which three primary germ layers are established [2]. Mouse early embryos include a population of pluripotent cells which were cultured with fibroblast feeder cells in vitro to form embryonic stem cells (ESCs) [5,6]. The gene expression pattern of ESCs is heterogeneous when they are cultured in serum and leukaemia inhibitory factor (LIF) without feeders [9]; their gene
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