miR-24 affects hair follicle morphogenesis targeting Tcf-3.
During embryonic development, hair follicles (HFs) develop from an epidermal-mesenchymal cross talk between the ectoderm progenitor layer and the underlying dermis. Epidermal stem cell activation represents a crucial point both for HF morphogenesis and for hair regeneration. miR-24 is an anti-proliferative microRNA (miRNA), which is induced during differentiation of several cellular systems including the epidermis. Here, we show that miR-24 is expressed in the HF and has a role in hair morphogenesis. We generated transgenic mice ectopically expressing miR-24 under the K5 promoter. The K5::miR-24 animals display a marked defect in HF morphogenesis, with thinning of hair coat and altered HF structure. Expression of miR-24 alters the normal process of hair keratinocyte differentiation, leading to altered expression of differentiation markers. MiR-24 directly represses the hair keratinocyte stemness regulator Tcf-3. These results support the notion that microRNAs, and among them miR-24, have an important role in postnatal epidermal homeostasis.
1] Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, Leicester, UK [2] Biochemistry Laboratory IDI-IRCCS and University of Rome 'Tor Vergata', Department of Experimental Medicine and Biochemical Sciences, Rome 00133, Italy.
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Amelio
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Lena
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Bonanno
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Melino
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Candi
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D018859:Hair Follicle / Q000166:cytology*; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058125:Transcription Factor 7-Like 1 Protein / Q000235:genetics / Q000378:metabolism*
D035683:MicroRNAs; C529080:Mirn24 microRNA, mouse; D058125:Transcription Factor 7-Like 1 Protein