Patterns of proliferation and apoptosis during murine hair follicle morphogenesis
Patterns of proliferation and apoptosis during murine hair follicle morphogenesis
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DOI：
10.1046/j.0022-202x.2001.01368.x
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发表时间：
2001-06-01
影响因子：
6.5
通讯作者：
Paus, R
中科院分区：
文献类型：
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作者：
Magerl, M;Tobin, DJ;Paus, R
在这项研究中，我们研究了新生小鼠毛囊形态发生过程中皮肤凋亡和增殖的关系，我们采用了一种新的三重染色技术，使用Ki67免疫反应性作为增殖标记，TUNEL和Hoechst 33342染色作为凋亡标记。我们还评估了白细胞介素-1 β转换酶、caspase 1（执行细胞凋亡的关键酶）和P-cadherin的免疫反应性，P-cadherin被认为是分离增殖角质形成细胞的关键粘附受体。将TUNEL数据与高分辨率光镜和透射电镜数据进行系统比较。实际上，发育中的毛芽中所有角质形成细胞Ki67（+）都呈强烈的阳性，这表明毛芽不是表皮内陷，而主要是局部角质形成细胞增殖的产物。随着毛囊发育的推进，三个明显的增殖灶变得明显：毛管周围的远端外根鞘、中端外根鞘和近端毛基质。在这些增殖的毛囊角质形成细胞中，只有特定的亚群表达p -钙粘蛋白。在小鼠毛囊形态发生第5期之前，毛囊内未发现TUNEL+细胞。在毛囊发育的早期阶段，白细胞介素-1 β转换酶免疫反应性存在于所有角质形成细胞上，但随后在近端毛囊上皮上几乎消失。高分辨率光学显微镜/透射电镜显示，在整个毛囊发育过程中，包括其早期阶段，所有上皮性毛囊腔中都有分散和聚集的角化细胞凋亡。这突出了TUNEL技术和高分辨率光学显微镜/透射电子显微镜在毛囊角化细胞凋亡的划分上的显著差异，并表明凋亡在毛囊发育早期甚至在毛囊发育过程中也起着雕刻作用。
In this study, we have correlated cutaneous apoptosis and proliferation in neonatal mice during hair follicle morphogenesis, We have applied a novel triple-staining technique that uses Ki67 immunoreactivity as a marker of proliferation as well as TUNEL and Hoechst 33342 staining as apoptosis markers. We have also assessed the immunoreactivity of interleukin-1 beta -converting enzyme, caspase 1, a key enzyme in the execution of apoptosis, and of P-cadherin, which has been suggested as a key adhesion receptor in segregating proliferating keratinocytes. The TUNEL data were systematically compared with high resolution light microscopy and transmission electron microscopy data. Virtually all keratinocytes of the developing hair bud were strongly Ki67(+), suggesting that the hair bud is not an epidermal invagination but primarily the product of localized keratinocyte proliferation. As hair follicle development advanced, three distinct foci of proliferation became apparent: the distal outer root sheath around the hair canal, the mid outer root sheath, and the proximal hair matrix. Of these proliferating hair follicle keratinocytes only defined subsets expressed P-cadherin. TUNEL+ cells in the hair follicle were not found before stage 5 of murine hair follicle morphogenesis. During the early stages of hair follicle development, interleukin-1 beta -converting enzyme immunoreactivity was present on all keratinocytes, but virtually disappeared from the proximal hair follicle epithelium later on. High resolution light microscopy/transmission electron microscopy revealed scattered and clustered apoptotic keratinocytes in all epithelial hair follicle compartments throughout hair follicle development, including its earliest stages. This highlights striking differences in the demarcation of apoptotic hair follicle keratinocytes between the TUNEL technique and high resolution light microscopy/transmission electron microscopy and suggests a role for apoptosis in sculpting the hair follicle even during early hair follicle development.