title: Sox9 is essential for outer root sheath differentiation and the formation of the hair stem cell compartment.
abstract: BACKGROUND
  The mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle consists of several concentric epithelial sheaths with the outer root sheath (ORS) forming the outermost layer. Functionally, the ORS has been implicated in the migration of hair stem cells from the stem cell niche toward the hair bulb. However, factors required for the differentiation of this critical cell lineage remain to be identified. Here, we describe an unexpected role of the HMG-box-containing gene Sox9 in hair development.
  
  
  RESULTS
  Sox9 expression can be first detected in the epithelial component of the hair placode but then becomes restricted to the outer root sheath (ORS) and the hair stem cell compartment (bulge). Using tissue-specific inactivation of Sox9, we demonstrate that this gene serves a crucial role in hair differentiation and that skin deleted for Sox9 lacks external hair. Strikingly, the ORS acquires epidermal characteristics with ectopic expression of GATA3. Moreover, Sox9 knock hair show severe proliferative defects and the stem cell niche never forms. Finally, we show that Sox9 expression depends on sonic hedgehog (Shh) signaling and demonstrate overexpression in skin tumors in mouse and man.
  
  
  CONCLUSIONS
  We conclude that although Sox9 is dispensable for hair induction, it directs differentiation of the ORS and is required for the formation of the hair stem cell compartment. Our genetic analysis places Sox9 in a molecular cascade downstream of sonic hedgehog and suggests that this gene is involved in basal cell carcinoma.
authors.affiliation: INSERM U636, Centre de Biochimie, Faculté des Sciences, Parc Valrose, 06108 Nice, France.
authors.forename: Valerie P I
authors.initials: VP
authors.lastname: Vidal
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Chaboissier
authors.forename: Susanne
authors.initials: S
authors.lastname: Lützkendorf
authors.forename: George
authors.initials: G
authors.lastname: Cotsarelis
authors.forename: Pleasantine
authors.initials: P
authors.lastname: Mill
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Hui
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ortonne
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Ortonne
authors.forename: Andreas
authors.initials: A
authors.lastname: Schedl
mesh_terms: D000505:Alopecia / Q000235:genetics; D000818:Animals; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D018859:Hair Follicle / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D053823:Hedgehog Proteins; D006609:High Mobility Group Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D055758:SOX9 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D012878:Skin Neoplasms / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D050990:GATA3 Transcription Factor; D053823:Hedgehog Proteins; D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C465570:Shh protein, mouse; C527933:Sox9 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors