A role for PDGF signaling in expansion of the extra-embryonic endoderm lineage of the mouse blastocyst
A role for PDGF signaling in expansion of the extra-embryonic endoderm lineage of the mouse blastocyst
复制标题
DOI：
10.1242/dev.050864
复制
发表时间：
2010-10-15
期刊：
影响因子：
4.6
通讯作者：
Hadjantonakis, Anna-Katerina
中科院分区：
文献类型：
--
作者：
Artus, Jerome;Panthier, Jean-Jacques;Hadjantonakis, Anna-Katerina
哺乳动物胚泡的内细胞团（ICM）由多能性外胚层（EPI）和原始内胚层（PrE）两个谱系组成。我们已经确定了血小板衍生生长因子受体α（PDGFR）。作为PrE谱系及其衍生物在小鼠胚胎和胚胎外内胚层（ExEn）的离体范例中的早期标记。通过结合活成像的胚胎和胚胎来源的干细胞表达的组蛋白H2 B-GFP融合报告基因的控制下的Pdgfra调控元件与谱系特异性标记物的分析，我们发现，Pdgfra的表达与GATA 6，最早表达的PrE谱系的转录调节。我们表明，GATA 6是激活Pdgfra表达所必需的。使用药理学抑制和基因失活，我们解决了PDGF途径在PrE谱系中的作用。我们的研究结果表明，PDGF信号是必不可少的建立，并在增殖中发挥作用，XEN细胞，这是从小鼠囊胚期胚胎分离，并代表PrE谱系。植入Pdgfra突变囊胚表现出PrE细胞数量减少，延迟植入加剧了这种影响。令人惊讶的是，我们还注意到，在增殖延迟的Pdgfra无效突变体中，EPI细胞的数量增加。总之，我们的数据表明PDGF信号传导在ExEn谱系的扩展中的作用。我们的观察还揭示了PrE在调节多能EPI隔室的大小方面可能的作用。
The inner cell mass (ICM) of the implanting mammalian blastocyst comprises two lineages: the pluripotent epiblast (EPI) and primitive endoderm (PrE). We have identified platelet-derived growth factor receptor alpha (PDGFR.) as an early marker of the PrE lineage and its derivatives in both mouse embryos and ex vivo paradigms of extra-embryonic endoderm (ExEn). By combining live imaging of embryos and embryo-derived stem cells expressing a histone H2B-GFP fusion reporter under the control of Pdgfra regulatory elements with the analysis of lineage-specific markers, we found that Pdgfra expression coincides with that of GATA6, the earliest expressed transcriptional regulator of the PrE lineage. We show that GATA6 is required for the activation of Pdgfra expression. Using pharmacological inhibition and genetic inactivation we addressed the role of the PDGF pathway in the PrE lineage. Our results demonstrate that PDGF signaling is essential for the establishment, and plays a role in the proliferation, of XEN cells, which are isolated from mouse blastocyst stage embryos and represent the PrE lineage. Implanting Pdgfra mutant blastocysts exhibited a reduced number of PrE cells, an effect that was exacerbated by delaying implantation. Surprisingly, we also noted an increase in the number of EPI cells in implantation-delayed Pdgfra-null mutants. Taken together, our data suggest a role for PDGF signaling in the expansion of the ExEn lineage. Our observations also uncover a possible role for the PrE in regulating the size of the pluripotent EPI compartment.