Telophase correction refines division orientation in stratified epithelia
Telophase correction refines division orientation in stratified epithelia
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DOI：
10.7554/elife.49249
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发表时间：
2019-12-13
期刊：
影响因子：
7.7
通讯作者：
Williams, Scott E.
中科院分区：
文献类型：
--
作者：
Lough, Kendall J.;Byrd, Kevin M.;Williams, Scott E.
在器官发生过程中，纺锤体方向的精确控制平衡了增殖和分化。在发育中的小鼠表皮中，平面和垂直分裂分别产生对称和不对称的命运结果。传统上，分裂轴指定涉及中心体迁移和纺锤体旋转，这两个事件发生在有丝分裂的早期。在这里，我们确定了一种新的定向机制，它可以纠正末期错误的后期定向。重定向的方向性与根尖女儿保持或失去基底部接触有关。虽然已知支架蛋白LGN决定了最初的纺锤体位置，但我们发现LGN在终末期也发挥作用，将倾斜的分裂重新定向为垂直方向。端粒矫正的保真度还依赖于张力敏感型黏附连接蛋白vinculin、α-E-catenin和afadin。这种矫正机制的失败会影响组织结构，因为持续的斜裂会导致早熟、持续的分化。末期矫正提供的分裂方向可塑性可能使祖细胞适应局部组织的需要。
During organogenesis, precise control of spindle orientation balances proliferation and differentiation. In the developing murine epidermis, planar and perpendicular divisions yield symmetric and asymmetric fate outcomes, respectively. Classically, division axis specification involves centrosome migration and spindle rotation, events occurring early in mitosis. Here, we identify a novel orientation mechanism which corrects erroneous anaphase orientations during telophase. The directionality of reorientation correlates with the maintenance or loss of basal contact by the apical daughter. While the scaffolding protein LGN is known to determine initial spindle positioning, we show that LGN also functions during telophase to reorient oblique divisions toward perpendicular. The fidelity of telophase correction also relies on the tension-sensitive adherens junction proteins vinculin, alpha-E-catenin, and afadin. Failure of this corrective mechanism impacts tissue architecture, as persistent oblique divisions induce precocious, sustained differentiation. The division orientation plasticity provided by telophase correction may enable progenitors to adapt to local tissue needs.