The miRNA-processing enzyme dicer is essential for the morphogenesis and maintenance of hair follicles
The miRNA-processing enzyme dicer is essential for the morphogenesis and maintenance of hair follicles
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DOI：
10.1016/j.cub.2006.04.005
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发表时间：
2006-05-23
期刊：
影响因子：
9.2
通讯作者：
Millar, Sarah E.
中科院分区：
文献类型：
--
作者：
Andl, Thomas;Murchison, Elizabeth P.;Millar, Sarah E.
MicroRNAs(MiRNAs)通过转录后抑制在基因表达调控中发挥重要作用的发现揭示了一种以前未知的控制发育和祖细胞功能的机制(见文献[1，2])；然而，对miRNA在哺乳动物器官发生中的功能知之甚少。MiRNAs的加工及其组装成RNA诱导沉默(RISC)复合体需要必要的多功能酶Dager[1]。我们发现在小鼠皮肤中表达Dier mRNA和多个miRNAs，这表明在皮肤和毛囊生物学中发挥了作用。在新生的小鼠中，携带表皮特异的DICER缺失，毛囊发育迟缓和增殖不良。毛干和内根鞘开始分化，但突变的毛囊在出生后第7天失去了关键信号分子Shh和Notch1的表达。在这个阶段，毛囊真皮乳头外翻，在基表皮内形成非常不寻常的结构。该突变体不能产生正常的毛干，毛囊缺乏干细胞标记而退化。与滤泡增殖减少相反，表皮变得过度增殖。这些结果揭示了DICER在皮肤中的关键作用，并暗示了miRNAs在表皮和毛囊发育和功能的关键方面。
The discovery that microRNAs (miRNAs) play important roles in regulating gene expression via post-transcriptional repression has revealed a previously unsuspected mechanism controlling development and progenitor-cell function (reviewed in [1, 2]); however, little is known of miRNA functions in mammalian organogenesis. Processing of miRNAs, and their assembly into the RNA-induced silencing (RISC) complex requires the essential multifunctional enzyme Dicer [1]. We found that Dicer mRNA and multiple miRNAs are expressed in mouse skin, suggesting roles in skin- and hair-follicle biology. In newborn mice carrying an epidermal-specific Dicer deletion, hair follicles were stunted and hypoproliferative. Hair-shaft and inner-root-sheath differentiation was initiated, but the mutant hair follicles were misoriented and expression of the key signaling molecules Shh and Notch1 was lost by postnatal day 7. At this stage, hair-follicle dermal papillae were observed to evaginate, forming highly unusual structures within the basal epidermis. Normal hair shafts were not produced in the Dicer mutant, and the follicles lacked stem cell markers and degenerated. In contrast to decreased follicular proliferation, the epidermis became hyperproliferative. These results reveal critical roles for Dicer in the skin and implicate miRNAs in key aspects of epidermal and hair-follicle development and function.