Dlg1 controls planar spindle orientation in the neuroepithelium through direct interaction with LGN.
Dlg1 controls planar spindle orientation in the neuroepithelium through direct interaction with LGN.
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DOI：
10.1083/jcb.201405060
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发表时间：
2014-09-15
期刊：
影响因子：
--
通讯作者：
Morin X
中科院分区：
文献类型：
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作者：
Saadaoui M;Machicoane M;di Pietro F;Etoc F;Echard A;Morin X
Dlg1将LGN招募到鸡神经上皮细胞的皮质，并可能提供驱动平面纺锤体定向的指导性线索。定向细胞分裂对于上皮结构的发育是必要的。有丝分裂纺锤体的定向需要通过进化上保守的LGN复合体在细胞皮质精确定位作用力发生器。然而，在脊椎动物上皮细胞中，作用于该复合体上游的极性线索仍不清楚。在本文中，我们证明了Dlg1在有丝分裂过程中定位于基侧细胞皮质，并且是鸡神经上皮细胞平面纺锤体定位所必需的。实时成像显示，Dlg1在中期的定向纺锤体运动中是必需的。从力学上讲，我们证明了Dlg1和LGN之间的直接相互作用促进了LGN复合体的皮质定位。此外，在粘附性微图案上分裂的人类细胞中，均一定位的Dlg1将LGN招募到有丝分裂皮质，这也是正确的纺锤体定向所必需的。我们认为Dlg1主要作用是将LGN招募到皮质，Dlg1的定位可能还为纺锤体的定位提供了有益的线索。
Dlg1 recruits LGN to the cortex of cells in the chick neuroepithelium and may provide instructive cues that drive planar spindle orientation. Oriented cell divisions are necessary for the development of epithelial structures. Mitotic spindle orientation requires the precise localization of force generators at the cell cortex via the evolutionarily conserved LGN complex. However, polarity cues acting upstream of this complex in vivo in the vertebrate epithelia remain unknown. In this paper, we show that Dlg1 is localized at the basolateral cell cortex during mitosis and is necessary for planar spindle orientation in the chick neuroepithelium. Live imaging revealed that Dlg1 is required for directed spindle movements during metaphase. Mechanistically, we show that direct interaction between Dlg1 and LGN promotes cortical localization of the LGN complex. Furthermore, in human cells dividing on adhesive micropatterns, homogenously localized Dlg1 recruited LGN to the mitotic cortex and was also necessary for proper spindle orientation. We propose that Dlg1 acts primarily to recruit LGN to the cortex and that Dlg1 localization may additionally provide instructive cues for spindle orientation.