Asymmetric division of contractile domains couples cell positioning and fate specification.
Asymmetric division of contractile domains couples cell positioning and fate specification.
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DOI：
10.1038/nature18958
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发表时间：
2016-08-18
期刊：
影响因子：
64.8
通讯作者：
Hiiragi T
中科院分区：
文献类型：
--
作者：
Maître JL;Turlier H;Illukkumbura R;Eismann B;Niwayama R;Nédélec F;Hiiragi T
在植入前发育过程中，哺乳动物胚胎自组织形成囊胚，囊胚由包裹内细胞团（ICM）的上皮层组成，ICM产生所有胚胎组织。在小鼠中，定向细胞分裂、顶端-基底极性和肌动球蛋白收缩性被认为有助于ICM的形成。然而，这些进程如何协同工作仍不清楚。在这里，我们表明，顶端域的不对称分离产生具有不同收缩性的卵裂球，这触发了它们的排序到内部和外部的位置。胚胎形态发生的3D物理模型显示，只有当表面收缩性的差异超过可预测的阈值时，细胞才会内化。我们使用生物物理测量验证了这一预测，并使用母体肌球蛋白（Myh 9）敲除嵌合胚胎成功地在发育中的囊胚内重新定向细胞分选。最后，我们发现收缩力的丧失导致卵裂球显示ICM样标记，而不管它们的位置。特别是，收缩控制雅普亚细胞定位，提高了机械传感发生在胚泡谱系规范的可能性。我们的结论是，收缩夫妇的定位和命运规范的卵裂球。我们认为，这确保了强大的自我组织的卵裂球到囊胚，赋予显着的调节能力，哺乳动物胚胎。
During pre-implantation development, the mammalian embryo self-organizes into the blastocyst consisting of an epithelial layer encapsulating the inner-cell mass (ICM), which gives rise to all embryonic tissues. In mice, oriented cell division, apico-basal polarity and acto-myosin contractility are thought to contribute to the formation of the ICM. However, how these processes work in concert remains unclear. Here, we show that asymmetric segregation of the apical domain generates blastomeres with different contractility, which triggers their sorting into inner and outer positions. 3D physical modeling of embryo morphogenesis reveals that cells internalize only when differences in surface contractility exceed a predictable threshold. We validate this prediction using biophysical measurements and successfully re-direct cell sorting within the developing blastocyst using maternal myosin (Myh9) knockout chimeric embryos. Finally, we find that loss of contractility causes blastomeres to show ICM-like markers regardless of their position. In particular, contractility controls Yap sub-cellular localization, raising the possibility that mechanosensing occurs during blastocyst lineage specification. We conclude that contractility couples the positioning and fate specification of blastomeres. We propose that this ensures the robust self-organization of blastomeres into the blastocyst, which confers remarkable regulative capacities to mammalian embryos.