A role for borg5 during trophectoderm differentiation.
A role for borg5 during trophectoderm differentiation.
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DOI：
10.1002/stem.428
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发表时间：
2010-06
期刊：
影响因子：
5.2
通讯作者：
Zheng, Yixian
中科院分区：
文献类型：
--
作者：
Vong, Queenie P.;Liu, Zhonghua;Yoo, Jae Gyu;Chen, Rong;Xie, Wen;Sharov, Alexei A.;Fan, Chen-Ming;Liu, Chengyu;Ko, Minoru S. H.;Zheng, Yixian
干细胞分化伴随着逐渐的细胞形态发生和转录变化。鉴定在分化过程中控制细胞行为的形态调节因子可以阐明细胞形态发生如何与发育过程中的转录变化相结合。通过分析小鼠胚胎干细胞（ESCs）分化过程中的细胞行为，揭示了Borg 5（Rho鸟苷5′-三磷酸酶5的结合物）在滋养外胚层（TE）细胞形态发生中的调控作用。我们报告说，胚胎干细胞向TE的分化是伴随着增强肌动蛋白突起和细胞运动，需要上调Borg 5。Borg 5与Cdc 42和非典型蛋白激酶C（aPKC）相互作用，并在Cdc 42下游发挥功能以增强TE细胞运动性。Borg 5是体外分选TE向ESCs外分化所必需的。在发育中的胚胎中，Borg 5蛋白定位于细胞-细胞接触和压实后的细胞质。在桑椹胚和胚泡中，它在外部细胞中的表达水平高于内部细胞。Borg 5的减少破坏aPKC定位并抑制胚泡形成。由于Cdx 2和Borg 5促进彼此的表达，作为胚胎干细胞向TE分化，我们建议，细胞形态发生与转录变化相结合，以调节TE分化。我们的研究还证明了胚胎干细胞在识别对发育重要的形态调节因子方面的实用性。
Stem cell differentiation is accompanied by a gradual cellular morphogenesis and transcriptional changes. Identification of morphological regulators that control cell behavior during differentiation could shed light on how cell morphogenesis is coupled to transcriptional changes during development. By analyzing cellular behavior during differentiation of mouse embryonic stem cells (ESCs), we uncover a role of Borg5 (binder of Rho guanosine 5′-triphosphatase 5) in regulating trophectoderm (TE) cell morphogenesis. We report that differentiation of ESCs toward TE is accompanied by enhanced actin protrusion and cell motility that require upregulation of Borg5. Borg5 interacts with both Cdc42 and atypical protein kinase C (aPKC) and functions downstream of Cdc42 to enhance TE cell motility. Borg5 is required for the sorting of differentiating TE to the outside of ESCs in vitro. In developing embryos, Borg5 protein localizes to cell–cell contacts and the cytoplasm after compaction. It exhibits higher levels of expression in outer cells than in inner cells in morula and blastocysts. Reduction of Borg5 disrupts aPKC localization and inhibits blastocyst formation. Since Cdx2 and Borg5 facilitate each other's expression as ESCs differentiate toward TE, we propose that cell morphogenesis is coupled with transcriptional changes to regulate TE differentiation. Our studies also demonstrate the utility of ESCs in identifying morphological regulators important for development.
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