Paracrine action of FGF4 during periimplantation development maintains trophectoderm and primitive endoderm

Paracrine action of FGF4 during periimplantation development maintains trophectoderm and primitive endoderm
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DOI:
10.1002/gene.10192
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发表时间:
2003-05-01
期刊:
影响因子:
1.5
通讯作者:
Papaioannou, VE
Papaioannou, VE
中科院分区:
生物学4区
文献类型:
--
作者:
Goldin, SN;Papaioannou, VE

文献摘要

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FGF4是成纤维细胞生长因子(成纤维细胞生长因子)家族的成员,是围着床期小鼠发育所必需的,尽管其在这一阶段的确切作用尚不清楚。导致缺乏合子FGF4的胚胎移植后致死的缺陷的本质尚不清楚,对FGF4启动的信号下游靶标在囊胚的各个细胞室中的作用也知之甚少。在此,我们报告了FGF4(-/-)胚胎植入后的致死率不太可能严格反映对FGF4的有丝分裂要求。相反,我们的结果表明,FGF4在胚胎4.5天时需要维持滋养外胚层和原始内胚层的特性。这一结果与已报道的FGF4在维持滋养层干细胞方面的体外活性以及原始内胚层形成对受体酪氨酸激酶信号的要求是一致的。因此,Fgf4(-/-)胚胎植入后的致死性可能是由于胚外细胞类型未能正确分化和功能所致。(C)2003年Wiley-Liss,Inc.
FGF4, a member of the fibroblast growth factor (FGF) family, is absolutely required for periimplantation mouse development, although its precise role at this stage remains unknown. The nature of the defect leading to postimplantation lethality of embryos lacking zygotic FGF4 is unclear and little is known about downstream targets of FGF4-initiated signaling within the various cellular compartments of the blastocyst. Here we report that postimplantation lethality of Fgf4(-/-) embryos is unlikely to reflect strictly mitogenic requirements for FGF4. Rather, our results suggest that FGF4 is required to maintain trophectoderm and primitive endoderm identity at embryonic day 4.5. This result is consistent with the reported in vitro activity of FGF4 in maintaining trophoblast stem cells and with the requirement for receptor tyrosine kinase signaling in primitive endoderm formation. Thus, postimplantation lethality of Fgf4(-/-) embryos likely results from the failure of proper differentiation and function of extraembryonic cell types. (C) 2003 Wiley-Liss, Inc.