Polarity Reversal by Centrosome Repositioning Primes Cell Scattering during Epithelial-to-Mesenchymal Transition
Polarity Reversal by Centrosome Repositioning Primes Cell Scattering during Epithelial-to-Mesenchymal Transition
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DOI：
10.1016/j.devcel.2016.12.004
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发表时间：
2017-01-23
影响因子：
11.8
通讯作者：
Thery, Manuel
中科院分区：
文献类型：
--
作者：
Burute, Mithila;Prioux, Magali;Thery, Manuel
在上皮-间质转化 (EMT) 过程中，组织周边的细胞会破坏其内聚力，从而在组织内迁移。这种戏剧性的重组涉及静态上皮细胞的顶端基底极性到迁移间充质细胞的前后极性的重新定位，其特征不明确。为了研究细胞内重组与形态变化的空间协调，我们在体内、小鼠胚胎和乳腺发育过程中以及在体外培养的 3D 细胞聚集体和微图案细胞双联体中监测了 EMT 期间的中心体定位。在所有条件下，中心体从细胞间连接旁边的偏心位置移动到细胞核另一侧的细胞外基质粘附处，导致有效的内部极性反转。这一举措似乎得到了受控微管网络拆卸的支持。使用动态微模式连续释放细胞限制以及微管动力学的调节，证实中心体重新定位是细胞进一步脱离和分散的原因。
During epithelial-to-mesenchymal transition (EMT), cells lining the tissue periphery break up their cohesion to migrate within the tissue. This dramatic reorganization involves a poorly characterized reorientation of the apicobasal polarity of static epithelial cells into the front-rear polarity of migrating mesenchymal cells. To investigate the spatial coordination of intracellular reorganization with morphological changes, we monitored centrosome positioning during EMT in vivo, in developing mouse embryos and mammary gland, and in vitro, in cultured 3D cell aggregates and micropatterned cell doublets. In all conditions, centrosomes moved from their off-centered position next to intercellular junctions toward extracellular matrix adhesions on the opposite side of the nucleus, resulting in an effective internal polarity reversal. This move appeared to be supported by controlled micro tubule network disassembly. Sequential release of cell confinement using dynamic micropatterns, and modulation of microtubule dynamics, confirmed that centrosome repositioning was responsible for further cell disengagement and scattering.