A function for Rac1 in the terminal differentiation and pigmentation of hair
A function for Rac1 in the terminal differentiation and pigmentation of hair
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DOI：
10.1242/jcs.091868
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发表时间：
2012-02-15
影响因子：
4
通讯作者：
Haase, Ingo
中科院分区：
文献类型：
--
作者：
Behrendt, Kristina;Klatte, Jennifer;Haase, Ingo
小的GTCRac 1在表皮和毛囊的增殖和分化层中普遍表达。以前，Rac 1被证明可以调节这些隔室中的干细胞行为。此外，我们还研究了Rac 1在调节终末毛囊分化中是否具有特异的干细胞非依赖性功能。为了解决这个问题，我们表达了组成型活性突变体的Rac 1，L 61 Rac 1，只有在基底表皮层和外根鞘的小鼠具有表皮特异性缺失的内源性Rac 1，经历严重的脱发。由此产生的“救援”小鼠在其一生中都表现出被毛。因此，在皮肤的角蛋白-14阳性区室中Rac 1活性的表达足以形成正常量的毛囊和毛发。然而，救援小鼠中形成的毛发质量不正常。救援小鼠的被毛是灰色的，而野生型和L 61 Rac 1转基因小鼠的被毛是黑色的，有光泽。救援小鼠的毛发分析显示毛干和角质层的结构发生改变，髓质细胞的组织和色素分布受到干扰。髓质细胞的紊乱与皮质缺乏相关，通常从皮质突出到髓质的角蛋白填充的棘突。桥粒钙粘蛋白Dsc 2，通常装饰这些突起，被发现在救援小鼠的头发减少或不存在。我们的研究证明了Rac 1在毛发结构和色素沉着形成中的调节功能，从而首次确定了Rac 1在终末分化中的作用。
The small GTPase Rac1 is ubiquitously expressed in proliferating and differentiating layers of the epidermis and hair follicles. Previously, Rac1 was shown to regulate stem cell behaviour in these compartments. We have asked whether Rac1 has, in addition, a specific, stem-cell-independent function in the regulation of terminal hair follicle differentiation. To address this, we have expressed a constitutively active mutant of Rac1, L61Rac1, only in the basal epidermal layer and outer root sheath of mice possessing an epidermis-specific deletion of endogenous Rac1, which experience severe hair loss. The resulting 'rescue' mice exhibited a hair coat throughout their lives. Therefore, expression of Rac1 activity in the keratin-14-positive compartment of the skin is sufficient for the formation of hair follicles and hair in normal quantities. The quality of hair formed in rescue mice was, however, not normal. Rescue mice showed a grey, dull hair coat, whereas that of wild-type and L61Rac1-transgenic mice was black and shiny. Hair analysis in rescue mice revealed altered structures of the hair shaft and the cuticle and disturbed organization of medulla cells and pigment distribution. Disorganization of medulla cells correlates with the absence of cortical, keratin-filled spikes that normally protrude from the cortex into the medulla. The desmosomal cadherin Dsc2, which normally decorates these protrusions, was found to be reduced or absent in the hair of rescue mice. Our study demonstrates regulatory functions for Rac1 in the formation of hair structure and pigmentation and thereby identifies, for the first time, a role for Rac1 in terminal differentiation.