Epithelial Wnt ligand secretion is required for adult hair follicle growth and regeneration.
Epithelial Wnt ligand secretion is required for adult hair follicle growth and regeneration.
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DOI：
10.1038/jid.2012.230
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发表时间：
2013-01
影响因子：
6.5
通讯作者：
Atit, Radhika P.
中科院分区：
文献类型：
--
作者：
Myung, Peggy S.;Takeo, Makoto;Ito, Mayumi;Atit, Radhika P.
β-catenin是Wnt信号传导的关键分子，是成人毛囊生长和再生所必需的。然而，在生长原诱导过程中，Wnt/β-catenin激活所需的Wnt配体的细胞来源尚不清楚。在这项研究中，我们从基因上删除了Wnt-生产细胞分泌Wnt配体所需的基因Wntless，特别是在休止期毛囊上皮中。我们发现上皮Wnt配体是毛发生长所必需的，因为毛囊上皮中Wnt的缺失会导致毛发周期的严重停滞。与对照组毛囊相比，毛囊上皮和真皮乳头在毛发生长诱导过程中均显示Wnt/β-catenin信号明显减少。令人惊讶的是，负责头发再生的毛囊干细胞保持了干细胞标记物的表达，但增殖明显减少。最后，我们证明表皮Wnt配体对成人伤口诱导的新生毛发形成至关重要。总的来说，这些数据表明毛囊上皮分泌的Wnt配体是成人毛囊再生所必需的，并为治疗脱发等头发疾病的潜在细胞靶点提供了新的见解。
β-catenin, a key transducer molecule of Wnt signaling, is required for adult hair follicle growth and regeneration. However, the cellular source of Wnt ligands required for Wnt/β-catenin activation during anagen induction is unknown. In this study, we genetically deleted Wntless, a gene required for Wnt ligand secretion by Wnt-producing cells, specifically in the hair follicle epithelium during telogen phase. We show that epithelial Wnt ligands are required for anagen, as loss of Wntless in the follicular epithelium resulted in a profound hair cycle arrest. Both the follicular epithelium and dermal papilla showed markedly decreased Wnt/β-catenin signaling during anagen induction compared to control hair follicles. Surprisingly, hair follicle stem cells that are responsible for hair regeneration maintained expression of stem cell markers but exhibited significantly reduced proliferation. Finally, we demonstrate that epidermal Wnt ligands are critical for adult wound-induced de novo hair formation. Collectively, these data show that Wnt ligands secreted by the hair follicle epithelium are required for adult hair follicle regeneration and provide new insight into potential cellular targets for the treatment of hair disorders such as alopecia.
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