Circadian clock genes contribute to the regulation of hair follicle cycling.
Circadian clock genes contribute to the regulation of hair follicle cycling.
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昼夜节律基因有助于调节毛囊循环。
DOI：
10.1371/journal.pgen.1000573
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发表时间：
2009-07
期刊：
影响因子：
4.5
通讯作者：
Andersen B
中科院分区：
文献类型：
--
作者：
Lin KK;Kumar V;Geyfman M;Chudova D;Ihler AT;Smyth P;Paus R;Takahashi JS;Andersen B
毛囊经历受控生长（生长期）、退化（退化期）和相对静止（休止期）的周期性循环，具有确定的周期性。采用基因组学方法研究同步小鼠毛囊周期中的基因表达，我们发现，除了昼夜节律波动外，时钟调节基因也与毛发生长周期同步调节。在生长终期和生长初期，生物钟基因在次级毛胚中显著表达，其中含有生长毛囊的前体细胞。Clock和Bmal 1突变小鼠的分析揭示了生长期进展的延迟，并且次级毛生殖细胞显示磷酸化Rb水平降低并且缺乏有丝分裂细胞，这表明生物钟基因通过其对细胞周期的影响来调节生长期进展。与细胞周期G1期阻滞一致，我们发现Bmal1突变皮肤中p21显著上调。虽然昼夜节律钟机制已被牵连在各种昼夜生物过程中，我们的研究结果表明，昼夜节律钟基因可用于调节非昼夜周期性过程的进展。毛囊通过在生长、退化和静止阶段之间反复循环来更新自身。毛囊循环的一个功能是允许头发生长的季节性变化。了解毛囊周期的调节也很有趣，因为毛发周期控制基因的异常调节是导致多种类型的人类毛发生长障碍和皮肤癌的原因。我们在这里报告说，控制昼夜节律的Clock和Bmal1基因对毛囊周期的调节也很重要，毛囊周期是一个持续时间比24小时长得多的生物学过程。对中央时钟基因突变小鼠皮肤的详细分析表明，毛发生长阶段的进展显着延迟。我们发现，时钟基因影响关键细胞周期控制基因的表达，Bmal 1突变小鼠毛囊关键区室中的角质形成细胞停止在细胞周期的G1期。这些发现提供了新的见解昼夜节律控制机制，在不同的时间尺度上调节循环生物过程的进展。
Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK–regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes. The hair follicle renews itself by repeatedly cycling among growth, regression, and rest phases. One function of hair follicle cycling is to allow seasonal changes in hair growth. Understanding the regulation of hair follicle cycling is also of interest because abnormal regulation of hair cycle control genes is responsible for several types of human hair growth disorders and skin cancers. We report here that Clock and Bmal1 genes, which control circadian rhythms, are also important for the regulation of hair follicle cycling, a biological process of much longer duration than 24 hours. Detailed analysis of skin from mice mutated for central clock genes indicates a significant delay in the progression of the hair growth phase. We show that clock genes affect the expression of key cell cycle control genes and that keratinocytes in a critical compartment of the hair follicles in Bmal1 mutant mice are halted in the G1 phase of the cell cycle. These findings provide novel insight into circadian control mechanisms in modulating the progression of cyclic biological processes on different time scales.
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影响因子：
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作者：
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通讯作者：
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