Vidal Valerie P I, Chaboissier Marie-Christine, Lützkendorf Susanne, Cotsarelis George, Mill Pleasantine, Hui Chi-Chung, Ortonne Nicolas, Ortonne Jean-Paul, Schedl Andreas
INSERM U636, Centre de Biochimie, Faculté des Sciences, Parc Valrose, 06108 Nice, France.
Curr Biol. 2005 Aug 9;15(15):1340-51. doi: 10.1016/j.cub.2005.06.064.
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.
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.
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.
哺乳动物的毛发是理解发育过程和干细胞生物学的无与伦比的模型系统。毛囊由几个同心上皮鞘组成，外根鞘（ORS）形成最外层。在功能上，外根鞘与毛干细胞从干细胞龛向毛球的迁移有关。然而，这个关键细胞谱系分化所需的因素仍有待确定。在这里，我们描述了含HMG盒基因Sox9在毛发发育中的意外作用。
Sox9的表达首先可在毛基板的上皮成分中检测到，但随后局限于外根鞘（ORS）和毛干细胞区室（隆突）。通过组织特异性敲除Sox9，我们证明该基因在毛发分化中起关键作用，且缺失Sox9的皮肤没有外部毛发。引人注目的是，外根鞘通过GATA3的异位表达获得表皮特征。此外，Sox9敲除的毛发显示出严重的增殖缺陷，且干细胞龛从未形成。最后，我们表明Sox9的表达依赖于音猬因子（Shh）信号，并在小鼠和人类的皮肤肿瘤中显示过表达。
我们得出结论，虽然Sox9对于毛发诱导并非必需，但它指导外根鞘的分化，并且是毛干细胞区室形成所必需的。我们的基因分析将Sox9置于音猬因子下游的分子级联中，并表明该基因参与基底细胞癌。
