Distinct Requirements for FGFR1 and FGFR2 in Primitive Endoderm Development and Exit from Pluripotency.
Distinct Requirements for FGFR1 and FGFR2 in Primitive Endoderm Development and Exit from Pluripotency.
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FGFR1和FGFR2在原始内胚层开发中的不同要求，并退出多能。
DOI：
10.1016/j.devcel.2017.05.004
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发表时间：
2017-06-05
影响因子：
11.8
通讯作者：
Soriano P
中科院分区：
文献类型：
--
作者：
Molotkov A;Mazot P;Brewer JR;Cinalli RM;Soriano P
在小鼠胚胎着床前发育过程中，Fgf信号通路的激活对于内细胞群的分化和原始内胚层（PrE）的形成至关重要。我们现在使用荧光报告基因敲入细胞系表明，Fgfr1在囊胚的所有细胞群中表达，而Fgfr2的表达仅限于胚外细胞系，包括PrE。我们进一步表明，这两种受体的缺失会阻止PrE的发育，并证明Fgfr1在这一过程中比Fgfr2发挥更突出的作用。最后，我们证明了Fgfrs在胚胎干细胞分化中的重要作用，Fgfr1在胚胎干细胞从多能状态退出的过程中也比Fgfr2具有更大的影响。总的来说，这些结果确定了Fgf信号在植入前发育过程中调节内细胞质量（ICM）谱系限制和细胞承诺的机制。已知Fgf4/Erk信号在着床前阶段调节原始内胚层发育。Molotkov等人表明，Fgfr1和Fgfr2在这一过程中都是必需的，其中Fgfr1起主导作用。胚胎干细胞中的Fgfr1信号是退出多能性和达到启动状态所必需的。
Activation of the Fgf signaling pathway during preimplantation development of the mouse embryo is known to be essential for differentiation of the inner cell mass and the formation of the primitive endoderm (PrE). We now show using fluorescent reporter knock-in lines that Fgfr1 is expressed in all cell populations of the blastocyst, while Fgfr2 expression becomes restricted to extraembryonic lineages, including the PrE. We further show that loss of both receptors prevents the development of the PrE and demonstrate that Fgfr1 plays a more prominent role in this process than Fgfr2. Last, we document an essential role for Fgfrs in ES cell differentiation, with again Fgfr1 having a larger influence than Fgfr2 in ES cell exit from the pluripotent state. Collectively, these results identify mechanisms through which Fgf signaling regulates inner cell mass (ICM) lineage restriction and cell commitment during preimplantation development. Fgf4/Erk signaling is known to regulate primitive endoderm development at preimplantation stages. Molotkov et al. show that Fgfr1 and Fgfr2 are both required for this process, with a predominant role for Fgfr1. Fgfr1 signaling in ES cells is required for exit from pluripotency and for attaining the primed state.
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影响因子：
10.5
作者：
Brewer JR;Molotkov A;Mazot P;Hoch RV;Soriano P
通讯作者：
Soriano P
影响因子：
5.2
作者：
Artus, Jerome;Kang, Minjung;Cohen-Tannoudji, Michel;Hadjantonakis, Anna-Katerina
通讯作者：
Hadjantonakis, Anna-Katerina
影响因子：
11.8
作者：
Kang M;Garg V;Hadjantonakis AK
通讯作者：
Hadjantonakis AK
影响因子：
10.5
作者：
Brewer JR;Mazot P;Soriano P
通讯作者：
Soriano P
DOI：
10.1073/pnas.95.9.5082
发表时间：
1998-04-28
影响因子：
11.1
作者：
Arman, E;Haffner-Krausz, R;Lonai, P
通讯作者：
Lonai, P