Blimp1 is a critical determinant of the germ cell lineage in mice
Blimp1 is a critical determinant of the germ cell lineage in mice
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DOI：
10.1038/nature03813
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发表时间：
2005-07-14
期刊：
影响因子：
64.8
通讯作者：
Surani, MA
中科院分区：
文献类型：
--
作者：
Ohinata, Y;Payer, B;Surani, MA
小鼠生殖细胞的命运在多能外胚层细胞中响应于来自胚外组织的信号而被诱导。大约40个创始人原始生殖细胞的规格和他们的分离体细胞邻居是重要的事件在早期发展。我们已经提出，在这一特化过程中的一个关键事件包括对邻近细胞所采用的体细胞程序的抑制。在这里，我们表明，Blimp1（也称为Prdm1），一个已知的转录抑制因子，在小鼠生殖细胞谱系的基础中具有关键作用，因为它的破坏导致在原始生殖细胞形成过程的早期阻断。Blimp1缺陷突变胚胎形成一个紧密的集群约20原始生殖细胞样细胞，这不能显示特征的迁移，增殖和同源异型盒基因，通常伴随着规范的原始生殖细胞的一致抑制。此外，我们的遗传谱系追踪实验表明，Blimp1阳性细胞起源于近端后上胚层细胞确实是谱系限制的原始生殖细胞前体。
Germ cell fate in mice is induced in pluripotent epiblast cells in response to signals from extraembryonic tissues. The specification of approximately 40 founder primordial germ cells and their segregation from somatic neighbours are important events in early development. We have proposed that a critical event during this specification includes repression of a somatic programme that is adopted by neighbouring cells. Here we show that Blimp1 ( also known as Prdm1), a known transcriptional repressor, has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation. Blimp1-deficient mutant embryos form a tight cluster of about 20 primordial germ cell-like cells, which fail to show the characteristic migration, proliferation and consistent repression of homeobox genes that normally accompany specification of primordial germ cells. Furthermore, our genetic lineage-tracing experiments indicate that the Blimp1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors.