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Asymmetric division of contractile domains couples cell positioning and fate specification

机译：收缩域的不对称划分耦合细胞定位和命运规范

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摘要

During pre-implantation development, the mammalian embryo self-organizes into the blastocyst, which consists of an epithelial layer encapsulating the inner-cell mass (ICM) giving rise to all embryonic tissues(1). In mice, oriented cell division, apicobasal polarity and actomyosin contractility are thought to contribute to the formation of the ICM2-5. However, how these processes work together remains unclear. Here we show that asymmetric segregation of the apical domain generates blastomeres with different contractilities, which triggers their sorting into inner and outer positions. Three-dimensional physical modelling 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 redirect cell sorting within the developing blastocyst using maternal myosin (Myh9)-knockout chimaeric embryos. Finally, we find that loss of contractility causes blastomeres to show ICM-like markers, regardless of their position. In particular, contractility controls Yap subcellular localization(6), 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.
机译：在植入前的发育过程中，哺乳动物胚胎会自组织成胚泡，胚泡由囊封内部细胞团（ICM）的上皮层组成，从而产生所有胚胎组织（1）。在小鼠中，定向细胞分裂，apapobasal极性和肌动球蛋白收缩被认为有助于ICM2-5的形成。但是，这些过程如何协同工作仍不清楚。在这里，我们显示了根部区域的不对称分离会产生具有不同收缩性的卵裂球，从而触发它们排列到内部和外部位置。胚胎形态发生的三维物理建模表明，仅当表面收缩力的差异超过可预测的阈值时，细胞才会内在化。我们使用生物物理测量结果验证了这一预测，并成功地使用母体肌球蛋白（Myh9）-敲除的嵌合胚胎将发育中的胚泡内的细胞分选成功重定向。最后，我们发现收缩力的丧失导致卵裂球显示出ICM样标记，无论其位置如何。特别是，收缩力控制Yap亚细胞定位（6），从而增加了在胚泡谱系指定期间发生机械传感的可能性。我们得出的结论是，可收缩性结合了卵裂球的定位和命运规范。我们建议，这确保卵裂球进入囊胚的强大的自组织能力，赋予哺乳动物胚胎非凡的调节能力。

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  • 来源
    《Nature》 |2016年第7616期|344-348|共5页
  • 作者

    Maitre Jean-Leon; Turlier Herve; Illukkumbura Rukshala; Eismann Bjoern; Niwayama Ritsuya; Nedelec Francois; Hiiragi Takashi;

  • 作者单位

    European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany|Inst Curie, CNRS, INSERM, U934,UMR 3215,Mech Mammalian Dev Grp, 26 Rue Ulm, Paris 05, France;

    European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany;

    European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany;

    European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany|Bioquant, Neuenheimer Feld 267, D-69120 Heidelberg, Germany;

    European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany;

    European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany;

    European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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