Afadin orients cell division to position the tubule lumen in developing renal tubules
Afadin orients cell division to position the tubule lumen in developing renal tubules
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DOI：
10.1242/dev.148908
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发表时间：
2017-10-01
期刊：
影响因子：
4.6
通讯作者：
Marciano, Denise K.
中科院分区：
文献类型：
--
作者：
Gao, Lei;Yang, Zhufeng;Marciano, Denise K.
在许多类型的小管中，管腔的连续性对管的功能至关重要，但小管如何在体内产生管腔连续性尚不清楚。我们最近发现，尽管其作用机制尚不清楚，但f -肌动蛋白结合蛋白afadin是发育肾小管的管腔连续性所必需的。在这里，我们证明了在细胞分裂过程中，有丝分裂纺锤体定向是管腔连续性所必需的。通过体外三维囊肿模型，我们发现黄嘌呤定位于纺锤极附近的细胞皮层，并定位有丝分裂纺锤体。在小管中，细胞分裂可能相对于两个轴：纵向和顶基。出乎意料的是，对早期发育的肾小管的体内检查显示，细胞分裂不是纵向（或平面极化）轴定向的。然而，细胞分裂方向垂直于顶基轴。体内缺乏黄嘌呤可导致肾小管中顶基细胞分裂的定向错误。综上所述，这些结果支持一个模型，即黄嘌呤通过指导顶基纺锤体方向来决定管腔的位置，从而导致连续的管腔和正常的小管形态形成。
In many types of tubules, continuity of the lumen is paramount to tubular function, yet how tubules generate lumen continuity in vivo is not known. We recently found that the F-actin-binding protein afadin is required for lumen continuity in developing renal tubules, though its mechanism of action remains unknown. Here, we demonstrate that afadin is required for lumen continuity by orienting the mitotic spindle during cell division. Using an in vitro 3D cyst model, we find that afadin localizes to the cell cortex adjacent to the spindle poles and orients the mitotic spindle. In tubules, cell division may be oriented relative to two axes: longitudinal and apical-basal. Unexpectedly, in vivo examination of early-stage developing nephron tubules reveals that cell division is not oriented in the longitudinal (or planar-polarized) axis. However, cell division is oriented perpendicular to the apical-basal axis. Absence of afadin in vivo leads to misorientation of apical-basal cell division in nephron tubules. Together, these results support a model whereby afadin determines lumen placement by directing apical-basal spindle orientation, resulting in a continuous lumen and normal tubule morphogenesis.