Sox9 is essential for outer root sheath differentiation and the formation of the hair stem cell compartment

Item Type:	Article
Title:	Sox9 is essential for outer root sheath differentiation and the formation of the hair stem cell compartment
Creators Name:	Vidal, V.P. and Chaboissier, M.C. and Luetzkendorf, S. and Cotsarelis, G. and Mill, P. and Hui, C.C. and Ortonne, N. and Ortonne, J.P. and Schedl, A.
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.
Keywords:	Alopecia, Basal Cell Carcinoma, Developmental Gene Expression Regulation, GATA3 Transcription Factor, Gene Silencing, Hair Follicle, Hedgehog Proteins, High Mobility Group Proteins, Immunohistochemistry, In Situ Hybridization, Scanning Electron Microscopy, Signal Transduction, Skin Neoplasms, Stem Cells, Trans-Activators, Transcription Factors, Transgenic Mice, Animals, Mice
Source:	Current Biology
ISSN:	0960-9822
Publisher:	Cell Press
Volume:	15
Number:	15
Page Range:	1340-1351
Date:	9 August 2005
Official Publication:	https://doi.org/10.1016/j.cub.2005.06.064
PubMed:	View item in PubMed

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