Villani Rehan, Hodgson Samantha, Legrand Julien, Greaney Jessica, Wong Ho Yi, Pichol-Thievend Cathy, Adolphe Christelle, Wainwight Brandon, Francois Mathias, Khosrotehrani Kiarash
The University of Queensland, UQ Centre for Clinical Research, Royal Brisbane Hospital, Herston Road, Herston, Brisbane 4029, Queensland, Australia.
The University of Queensland, UQ Diamantina Institute, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4102, Queensland, Australia.
Development. 2017 May 15;144(10):1887-1895. doi: 10.1242/dev.143917.
SOX family proteins SOX2 and SOX18 have been reported as being essential in determining hair follicle type; however, the role they play during development remains unclear. Here, we demonstrate that regulates the normal differentiation of the dermal papilla of all hair types. In guard (primary) hair dermal condensate (DC) cells, we identified transient in addition to SOX2 expression at E14.5, which allowed fate tracing of primary DC cells until birth. Similarly, expression of was detected in the DC cells of secondary hairs at E16.5 and in tertiary hair at E18.5. Dominant-negative mutation (opposum) did not prevent DC formation in any hair type. However, it affected dermal papilla differentiation, restricting hair formation especially in secondary and tertiary hairs. This mutation also prevented neonatal dermal cells or dermal papilla spheres from inducing hair in regeneration assays. Microarray expression studies identified WNT5A and TNC as potential downstream effectors of SOX18 that are important for epidermal WNT signalling. In conclusion, SOX18 acts as a mesenchymal molecular switch necessary for the formation and function of the dermal papilla in all hair types.
据报道，SOX家族蛋白SOX2和SOX18在决定毛囊类型方面至关重要；然而，它们在发育过程中所起的作用仍不清楚。在此，我们证明 调节所有毛发类型的真皮乳头的正常分化。在保卫（初级）毛的真皮凝聚物（DC）细胞中，我们在胚胎第14.5天除了检测到SOX2表达外，还鉴定出短暂的 ，这使得能够对初级DC细胞进行命运追踪直至出生。同样，在胚胎第16.5天的次级毛的DC细胞以及胚胎第18.5天的三级毛中检测到 的表达。显性负性 突变（opposum）并未阻止任何毛发类型中DC的形成。然而，它影响真皮乳头分化，限制毛发形成，尤其是在次级和三级毛发中。这种 突变还阻止了新生真皮细胞或真皮乳头球体在再生试验中诱导毛发。微阵列表达研究确定WNT5A和TNC是SOX18的潜在下游效应物，对表皮WNT信号传导很重要。总之，SOX18作为一种间充质分子开关，对所有毛发类型的真皮乳头的形成和功能是必需的。
