title: Hairless down-regulates expression of Msx2 and its related target genes in hair follicles.
abstract: 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 down-regulated expression of Foxn1 and Lef1, MSX2 target genes, in vivo as well as in vitro.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Lifesciences, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Bong-Kyu
authors.initials: BK
authors.lastname: Kim
authors.forename: Sungjoo K
authors.initials: SK
authors.lastname: Yoon
mesh_terms: D000818:Animals; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000235:genetics; D053263:Gene Regulatory Networks; D018859:Hair Follicle / Q000254:growth & development / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics; D051379:Mice; D008812:Mice, Hairless; D008817:Mice, Mutant Strains; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; C084119:MSX2 protein; D012333:RNA, Messenger; D014157:Transcription Factors; C090140:Whn protein; C088661:hr protein, mouse
keywords: Foxn1; HR; Hair follicle; Hairpoor; Lef1; Msx2