Proper spindle orientation is required for asymmetric cell division and the establishment of complex tissue architecture. In the developing epidermis, spindle orientation requires a conserved cortical protein complex of LGN/NuMA/dynein-dynactin. However, how microtubule dynamics are regulated to interact with this machinery and properly position the mitotic spindle is not fully understood. Furthermore, our understanding of the processes that link spindle orientation during asymmetric cell division to cell fate specification in distinct tissue contexts remains incomplete. We report a role for the microtubule catastrophe factor KIF18B in regulating microtubule dynamics to promote spindle orientation in keratinocytes. During mitosis, KIF18B accumulates at the cell cortex, colocalizing with the conserved spindle orientation machinery. In vivo we find that KIF18B is required for oriented cell divisions within the hair placode, the first stage of hair follicle morphogenesis, but is not essential in the interfollicular epidermis. Disrupting spindle orientation in the placode, using mutations in either KIF18B or NuMA, results in aberrant cell fate marker expression of hair follicle progenitor cells. These data functionally link spindle orientation to cell fate decisions during hair follicle morphogenesis. Taken together, our data demonstrate a role for regulated microtubule dynamics in spindle orientation in epidermal cells. This work also highlights the importance of spindle orientation during asymmetric cell division to dictate cell fate specification.

不对称细胞分裂和复杂组织结构的建立需要正确的纺锤体方向。在发育中的表皮中，纺锤体方向需要 LGN/NuMA/dynein-dynactin 的保守皮质蛋白复合物。然而，如何调节微管动力学以与这种机制相互作用并正确定位有丝分裂纺锤体尚不完全清楚。此外，我们对将不对称细胞分裂过程中纺锤体方向与不同组织环境中细胞命运规范联系起来的过程的理解仍然不完整。我们报告了微管突变因子 KIF18B 在调节微管动力学以促进角质形成细胞纺锤体定向中的作用。在有丝分裂期间，KIF18B 在细胞皮层积累，与保守的纺锤体定向机器共定位。在体内，我们发现 KIF18B 是毛囊内定向细胞分裂所必需的，毛囊形态发生的第一阶段，但在毛囊间表皮中不是必需的。使用 KIF18B 或 NuMA 中的突变破坏基板中的纺锤体方向，导致毛囊祖细胞的细胞命运标记表达异常。这些数据在功能上将纺锤体方向与毛囊形态发生过程中的细胞命运决定联系起来。总之，我们的数据证明了调节微管动力学在表皮细胞纺锤体方向中的作用。这项工作还强调了不对称细胞分裂过程中纺锤体方向对决定细胞命运规范的重要性。