FGF4 is a limiting factor controlling the proportions of primitive endoderm and epiblast in the ICM of the mouse blastocyst

FGF4 is a limiting factor controlling the proportions of primitive endoderm and epiblast in the ICM of the mouse blastocyst
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DOI:
10.1016/j.ydbio.2013.09.023
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发表时间:
2013-12-01
影响因子:
2.7
通讯作者:
Yamanaka, Yojiro
Yamanaka, Yojiro
中科院分区:
生物学3区
文献类型:
--
作者:
Krawchuk, Dayana;Honma-Yamanaka, Nobuko;Yamanaka, Yojiro

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原始内胚层(PE)和上胚层(EPI)是E3.5囊胚内细胞团(ICM)的两个谱系。尽管已经表明FGF信号传导对于ICM中的PE特化是必要且充分的,但尚不清楚是什么机制控制胚胎中的PE/EPI比例。由于单独调节FGF信号足以将所有ICM细胞转化为PE或EPI,因此已经提出了一种模型,其中胚胎中FGF的量控制PE/EPI比例。为了测试这个模型,我们使用各种基因型的Fgf 4突变体减少了着床前胚胎中主要的FGF 4的量。我们观察到Fgf 4在PE特化中的母体贡献,但其对发育的影响不大。此外,在用外源性FGF 4处理FGF 4突变体胚胎后,我们观察到PE比例以FGF 4剂量依赖性方式进行性增加,与胚胎基因型无关。我们的结论是FGF 4的量是有限的,并调节小鼠胚胎中PE/EPI的比例。(C)2013作者由爱思唯尔公司出版All rights reserved.
The primitive endoderm (PE) and epiblast (EPI) are two lineages derived from the inner cell mass (ICM) of the E3.5 blastocyst. Although it has been shown that FGF signaling is necessary and sufficient for PE specification in the ICM, it is unknown what mechanisms control the PE/EPI proportion in the embryo. Because modulation of FGF signaling alone is sufficient to convert all ICM cells to either PE or EPI, a model has been proposed in which the amount of FGF in the embryo controls the PE/EPI proportion. To test this model, we reduced the amount of FGF4, the major FGF in the preimplantation embryo, using various genotypes of Fgf4 mutants. We observed a maternal contribution of Fgf4 in PE specification, but it was dispensable for development. In addition, upon treatment of Fgf4 mutant embryos with exogenous FGF4, we observed a progressive increase of PE proportions in an FGF4 dose dependent manner, regardless of embryo genotype. We conclude that the amount of FGF4 is limited and regulates PE/EPI proportions in the mouse embryo. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.