Hairless down-regulates expression of Msx2 and its related target genes in hair follicles

Background: Hairless (HR), a transcriptional cofactor, plays important roles in hair follicle (HF) morphogenesis and cycling. Recently, we reported the new Hr mutant mouse called Hairpoor (Hr(Hp)) that causes HR overexpression through translational de-repression. The Msh homeobox 2 (Msx2) is a homolog of the Drosophila muscle segment homeobox (msh) gene, which expressed in the hair bulb, including in the germinal matrix, and its expression spreads into the upper region of the HF including the hair cortex. Objective: Although Msx2 is regarded as an important gene in hair cycle control and hair shaft differentiation, the regulation of Msx2 expression is not well-known. Methods: Using realtime polymerase chain reaction (PCR) and western blot, we investigated the relationship between HR and Msx2 in the Hr(Hp)/Hr(Hp) mouse during the HF morphogenesis. Immunohistochemistry was performed to compare the pattern of expression of MSX2 in Hr(Hp)/Hr(Hp) mouse skin with that in wild-type skin. Msx2 mRNA expression and promoter activity was estimated using a transient expression system to see whether HR down-regulates Msx2 expression in vitro. We also investigated whether downregulation of MSX2 by HR also affects the MSX2 regulatory pathway in the Hr(Hp)/Hr(Hp) mouse and in an in vitro system. Results: We found that the expression of Msx2 was down-regulated by HR, which in turn downregulated expression of Foxn1 and Lef1, MSX2 target genes, in vivo as well as in vitro. Conclusion: Our results show that HR regulates expression of genes in the MSX2 regulatory pathway, which explains abnormal HF formation in Hr(Hp)/Hr(Hp) skin. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.