Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway
Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway
复制标题
DOI：
10.1016/j.devcel.2006.02.020
复制
发表时间：
2006-05-01
影响因子：
11.8
通讯作者：
Rossant, Janet
中科院分区：
文献类型：
--
作者：
Chazaud, Claire;Yamanaka, Yojiro;Rossant, Janet
人们认为早期内细胞团（ICM）是一个同质群体，ICM中的细胞位置导致E4.5形成两个谱系，即上胚层（EPI）和原始内胚层（PE）。然而，在这里，我们表明，在E3.5的ICM已经是异质的。EPI和PE特异性转录因子Nanog和Gata 6早在E3.5就以相互排斥的方式以随机的“盐和胡椒”模式在ICM中表达。谱系追踪显示，E3.5时单个ICM细胞的主要谱系限制为任一谱系。在没有PE形成的缺乏Grb 2的胚胎中，Gata 6表达丢失，所有ICM细胞均为Nanog阳性。我们提出了一个模型，其中ICM发展为E3.5时EPI和PE祖细胞的马赛克，依赖于Grb 2-Ras-MAP激酶信号传导，随后将祖细胞分离到适当的细胞层中。
It has been thought that early inner cell mass (ICM) is a homogeneous population and that cell position in the ICM leads to the formation of two lineages, epiblast (EPI) and primitive endoderm (PE), by E4.5. Here, however, we show that the ICM at E3.5 is already heterogeneous. The EPI- and PE-specific transcription factors, Nanog and Gata6, were expressed in the ICM in a random "salt and pepper" pattern, as early as E3.5, in a mutually exclusive manner. Lineage tracing showed predominant lineage restriction of single ICM cells at E3.5 to either lineage. In embryos lacking Grb2 where no PE forms, Gata6 expression was lost and all ICM cells were Nanog positive. We propose a model in which the ICM develops as a mosaic of EPI and PE progenitors at E3.5, dependent on Grb2-Ras-MAP kinase signaling, followed by later segregation of the progenitors into the appropriate cell layers.