Department of Dermatology, Columbia University, New York, NY, USA.
PLoS Genet. 2012;8(11):e1003002. doi: 10.1371/journal.pgen.1003002. Epub 2012 Nov 1.
Hereditary hypertrichoses are a group of hair overgrowth syndromes that are extremely rare in humans. We have previously demonstrated that a position effect on TRPS1 is associated with hypertrichosis in humans and mice. To gain insight into the functional role of Trps1, we analyzed the late morphogenesis vibrissae phenotype of Trps1(Δgt) mutant mice, which is characterized by follicle degeneration after peg downgrowth has been initiated. We found that Trps1 directly represses expression of the hair follicle stem cell regulator Sox9 to control proliferation of the follicle epithelium. Furthermore, we identified a copy number variation upstream of SOX9 in a family with hypertrichosis that significantly decreases expression of the gene in the hair follicle, providing new insights into the long-range regulation of SOX9. Our findings uncover a novel transcriptional hierarchy that regulates epithelial proliferation in the developing hair follicle and contributes to the pathology of hypertrichosis.
遗传性多毛症是一组极为罕见的人类毛发过度生长综合征。我们之前的研究表明，TRPS1 的位置效应与人类和小鼠的多毛症有关。为了深入了解 Trps1 的功能作用，我们分析了 Trps1(Δgt) 突变小鼠的晚期形态发生触须表型，其特征是在 peg 向下生长启动后毛囊退化。我们发现 Trps1 直接抑制毛囊干细胞调节因子 Sox9 的表达，以控制毛囊上皮的增殖。此外，我们在一个多毛症家族中鉴定到 Sox9 上游的一个拷贝数变异，该变异显著降低了毛囊中基因的表达，为 Sox9 的远程调控提供了新的见解。我们的研究结果揭示了一个新的转录层次结构，该结构调节发育中的毛囊上皮细胞的增殖，并导致多毛症的病理学改变。
