An essential role for dermal primary cilia in hair follicle morphogenesis.

An essential role for dermal primary cilia in hair follicle morphogenesis.
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DOI:
10.1038/jid.2008.279
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发表时间:
2009-02
期刊:
The Journal of investigative dermatology
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其他
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初级纤毛是一种基于微管的细胞器,是许多信号通路的重要组成部分。它存在于整个哺乳动物体内的细胞中;然而,它在大多数组织中的功能仍然很大程度上未知。在此,我们证明初级纤毛在整个形态发生和出生后毛囊循环期间存在于小鼠皮肤和毛囊的细胞上。使用 Cre-lox 系统,我们破坏了腹侧真皮中的纤毛组装,并评估了其对毛囊发育的影响。真皮纤毛受损的小鼠受影响区域有严重的少毛症(缺乏毛发)。组织学分析表明,突变体中的大多数毛囊在毛发发育的第二阶段停滞,并且具有少量或不存在真皮凝结物。这种表型让人想起缺乏 Shh 或 Gli2 的小鼠皮肤中所见的表型。原位杂交和定量 RT-PCR 分析表明,hedgehog 通路在纤毛突变毛囊的真皮中下调。因此,这些数据表明纤毛是正常毛发形态发生所需的关键信号成分,并表明真皮细胞需要这种细胞器来接收信号,例如声波刺猬。
The primary cilium is a microtubule-based organelle implicated as an essential component of a number of signaling pathways. It is present on cells throughout the mammalian body; however, its functions in most tissues remain largely unknown. Herein we demonstrate that primary cilia are present on cells in murine skin and hair follicles throughout morphogenesis and during hair follicle cycling in postnatal life. Using the Cre-lox system, we disrupted cilia assembly in the ventral dermis and evaluated the effects on hair follicle development. Mice with disrupted dermal cilia have severe hypotrichosis (lack of hair) in affected areas. Histological analyses reveal that most follicles in the mutants arrest at stage 2 of hair development and have small or absent dermal condensates. This phenotype is reminiscent of that seen in the skin of mice lacking Shh or Gli2. In situ hybridization and quantitative RT-PCR analysis indicates that the hedgehog pathway is downregulated in the dermis of the cilia mutant hair follicles. Thus, these data establish cilia as a critical signaling component required for normal hair morphogenesis and suggest that this organelle is needed on cells in the dermis for reception of signals such as sonic hedgehog.
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