Asymmetric cell divisions promote stratification and differentiation of mammalian skin
Asymmetric cell divisions promote stratification and differentiation of mammalian skin
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DOI：
10.1038/nature03922
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发表时间：
2005-09-08
期刊：
影响因子：
64.8
通讯作者：
Fuchs, E
中科院分区：
文献类型：
--
作者：
Lechler, T;Fuchs, E
表皮是复层鳞状上皮，形成排除有害微生物并保留体液的屏障。为了执行这些功能，最内层的增殖基底细胞周期性地与细胞外基质的基底膜分离，向外移动并最终死亡。一旦达到基底上层，细胞就会停止分裂并进入分化程序以形成屏障(1)。人们对分层的机制知之甚少。尽管体外研究表明分层是通过表皮细胞的分层和随后的运动而发生的(2-4)，但大多数培养条件有利于缺乏组织中基底角质形成细胞极性和立方形形态的角质形成细胞。这些特征在考虑替代机制时可能很重要，即通过不对称细胞分裂发生分层，其中有丝分裂纺锤体垂直于基底膜定向(5-7)。在这里，我们表明基底表皮细胞利用其极性进行不对称分裂，产生定型基底上细胞和增殖性基底细胞。我们进一步证明，整合素和钙粘蛋白对于非典型蛋白激酶 C、Par3 - LGN - Inscuteable 复合物和 NuMA - dynactin 的顶端定位以对齐纺锤体至关重要。
The epidermis is a stratified squamous epithelium forming the barrier that excludes harmful microbes and retains body fluids. To perform these functions, proliferative basal cells in the innermost layer periodically detach from an underlying basement membrane of extracellular matrix, move outward and eventually die. Once suprabasal, cells stop dividing and enter a differentiation programme to form the barrier(1). The mechanism of stratification is poorly understood. Although studies in vitro have led to the view that stratification occurs through the delamination and subsequent movement of epidermal cells(2-4), most culture conditions favour keratinocytes that lack the polarity and cuboidal morphology of basal keratinocytes in tissue. These features could be important in considering an alternative mechanism, that stratification occurs through asymmetric cell divisions in which the mitotic spindle orients perpendicularly to the basement membrane(5-7). Here we show that basal epidermal cells use their polarity to divide asymmetrically, generating a committed suprabasal cell and a proliferative basal cell. We further demonstrate that integrins and cadherins are essential for the apical localization of atypical protein kinase C, the Par3 - LGN - Inscuteable complex and NuMA - dynactin to align the spindle.