Morphogenetic forces planar polarize LGN/Pins in the embryonic head during Drosophila gastrulation

Spindle orientation is often achieved by a complex of Partner of Inscuteable (Pins)/LGN, Mushroom Body Defect (Mud)/Nuclear Mitotic Apparatus (NuMa), Gαi, and Dynein, which interacts with astral microtubules to rotate the spindle. Cortical Pins/LGN recruitment serves as a critical step in this process. Here, we identify Pins-mediated planar cell polarized divisions in several of the mitotic domains of the early Drosophila embryo. We found that neither planar cell polarity pathways nor planar polarized myosin localization determined division orientation; instead, our findings strongly suggest that Pins planar polarity and force generated from mesoderm invagination are important. Disrupting Pins polarity via overexpression of a myristoylated version of Pins caused randomized division angles. We found that disrupting forces through chemical inhibitors, depletion of an adherens junction protein, or blocking mesoderm invagination disrupted Pins planar polarity and spindle orientation. Furthe..., ,纺锤体定向通常由Inscuteable伴侣蛋白（Partner of Inscuteable，Pins）/LGN、蕈形体缺陷蛋白（Mushroom Body Defect，Mud）/核有丝分裂器蛋白（Nuclear Mitotic Apparatus，NuMa）、Gαi以及动力蛋白（Dynein）组成的复合物介导，该复合物可与星型微管相互作用以旋转纺锤体。皮层Pins/LGN的招募是该过程中的关键步骤。本研究在早期果蝇胚胎的多个有丝分裂域中，鉴定出了Pins介导的平面细胞极性分裂。我们发现，平面细胞极性通路以及平面极性肌球蛋白定位均不决定分裂定向；相反，我们的研究结果强烈表明，Pins的平面极性以及中胚层内陷产生的牵引力发挥了重要作用。通过过表达肉豆蔻酰化形式的Pins以破坏Pins的极性，会导致分裂角度随机化。我们还发现，通过化学抑制剂处理、耗竭黏着连接蛋白或阻断中胚层内陷来破坏牵引力，会扰乱Pins的平面极性与纺锤体定向。此外……