PDGF signaling is required for primitive endoderm cell survival in the inner cell mass of the mouse blastocyst.

PDGF signaling is required for primitive endoderm cell survival in the inner cell mass of the mouse blastocyst.
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DOI:
10.1002/stem.1442
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发表时间:
2013-09
期刊:
影响因子:
5.2
通讯作者:
Hadjantonakis, Anna-Katerina
Hadjantonakis, Anna-Katerina
中科院分区:
医学2区
文献类型:
--
作者:
Artus, Jerome;Kang, Minjung;Cohen-Tannoudji, Michel;Hadjantonakis, Anna-Katerina

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在植入前期结束时,小鼠囊胚的内细胞团(ICM)由两种不同的细胞谱系组成,即多能外胚层(EPI)和原始内胚层(PrE)。目前的模型,其形成涉及最初的共表达的谱系特异性标记物,然后相互排斥的表达,导致在盐和胡椒分布的谱系前体内的ICM。继谱系定型之后,细胞重排和选择性凋亡被认为是驱动和细化两个空间上不同的区室出现的关键过程。在这里,我们已经解决了在小鼠胚胎发育早期的程序性细胞死亡的调节PDGF信号的作用。通过结合遗传学和药理学的方法,我们证明了缺乏PDGF活性的胚胎表现出半胱天冬酶依赖的PrE细胞选择性凋亡。调节PDGF活性并不影响谱系定型或细胞分选,这表明PDGF参与了模式信息的微调。我们的研究结果还表明,PDGF和FGF酪氨酸激酶受体发挥不同的和非重叠的功能PrE的形成。总之,这些数据揭示了在PrE和EPI细胞分离时PDGF信号传导在PrE细胞存活中的早期作用。
At the end of the preimplantation period, the inner cell mass (ICM) of the mouse blastocyst is composed of two distinct cell lineages, the pluripotent epiblast (EPI) and the primitive endoderm (PrE). The current model for their formation involves initial co-expression of lineage-specific markers followed by mutual-exclusive expression resulting in a salt-and-pepper distribution of lineage precursors within the ICM. Subsequent to lineage commitment, cell rearrangements and selective apoptosis are thought to be key processes driving and refining the emergence of two spatially distinct compartments. Here, we have addressed a role for PDGF signaling in the regulation of programmed cell death during early mouse embryonic development. By combining genetic and pharmacological approaches, we demonstrate that embryos lacking PDGF activity exhibited caspase-dependent selective apoptosis of PrE cells. Modulating PDGF activity did not affect lineage commitment or cell sorting, suggesting that PDGF is involved in the fine-tuning of patterning information. Our results also indicate that PDGF and FGF tyrosine kinase receptors exert distinct and non-overlapping functions in PrE formation. Taken together, these data uncover an early role of PDGF signaling in PrE cell survival at the time when PrE and EPI cells are segregated.
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