Centre de Biologie du Développement, Centre de Biologie Intégrative, Université Paul Sabatier/CNRS (Centre National de la Recherche Scientifique), Toulouse, France
Life Sci Alliance. 2019 Mar 28;2(2). doi: 10.26508/lsa.201900373. Print 2019 Apr.
In mammalian skin, ninein localizes to the centrosomes of progenitor cells and relocates to the cell cortex upon differentiation of keratinocytes, where cortical arrays of microtubules are formed. To examine the function of ninein in skin development, we use epidermis-specific and constitutive ninein-knockout mice to demonstrate that ninein is necessary for maintaining regular protein levels of the differentiation markers filaggrin and involucrin, for the formation of desmosomes, for the secretion of lamellar bodies, and for the formation of the epidermal barrier. Ninein-deficient mice are viable but develop a thinner skin with partly impaired epidermal barrier. We propose two underlying mechanisms: first, ninein contributes to spindle orientation during the division of progenitor cells, whereas its absence leads to misoriented cell divisions, altering the pool of progenitor cells. Second, ninein is required for the cortical organization of microtubules in differentiating keratinocytes, and for the cortical re-localization of microtubule-organizing proteins, and may thus affect any mechanisms that depend on localized microtubule-dependent transport.
在哺乳动物的皮肤中，ninenin 定位于祖细胞的中心体，并在角质形成细胞分化时重新定位到细胞皮层，在那里形成微管的皮质阵列。为了研究 ninein 在皮肤发育中的功能，我们使用表皮特异性和组成型 ninein 敲除小鼠来证明 ninein 对于维持分化标记物丝聚合蛋白和兜甲蛋白的正常蛋白水平、形成桥粒、分泌板层小体以及形成表皮屏障是必需的。缺乏 ninein 的小鼠是存活的，但皮肤较薄，表皮屏障部分受损。我们提出了两种潜在的机制：首先，ninenin 有助于祖细胞分裂期间纺锤体的定向，而其缺失会导致细胞分裂方向错误，改变祖细胞池。其次，ninenin 对于分化角质形成细胞中微管的皮质组织以及微管组织蛋白的皮质重新定位是必需的，因此可能会影响任何依赖于局部微管依赖性运输的机制。
