The Laboratory of Developmental Biology, The Azrieli Faculty of Medicine, Bar-Ilan university, Safed, Israel.
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum (DKFZ), 69120, Heidelberg, Germany.
Nat Commun. 2020 Oct 9;11(1):5114. doi: 10.1038/s41467-020-18643-x.
Tissue growth in the adult is an orchestrated process that often requires biological clocks to time stem cell and progenitor activity. Here, we employed the hair follicle, which cycles between growth and regression in a timely-restricted mode, to show that some components of the hair cycle clock reside within the mesenchymal niche of the hair follicle, the dermal papilla (DP), and both Fgf and Wnt signaling pathways interact within the DP to regulate the expression of these components that include Wnt agonists (Rspondins) and antagonists (Dkk2 and Notum). The levels of Wnt agonists and antagonists in the DP are progressively reduced and elevated during the growth phase, respectively. Consequently, Wnt signaling activity in the overlying epithelial progenitor cells decreases, resulting in the induction of the regression phase. Remarkably, DP properties allow Wnt activity in the DP to persist despite the Wnt-inhibiting milieu and consequently synchronize the induction and progression of the regression phase. This study provides insight into the importance of signaling crosstalk in coupling progenitors and their niche to regulate tissue growth.
成人组织生长是一个精心协调的过程，通常需要生物钟来控制干细胞和祖细胞的活动。在这里，我们利用毛囊在时间受限的模式下周期性地生长和退化，表明毛囊的间充质龛位（真皮乳头，DP）中存在一些毛发周期时钟的组成部分，Fgf 和 Wnt 信号通路在 DP 内相互作用，以调节这些组成部分的表达，包括 Wnt 激动剂（Rspondins）和拮抗剂（Dkk2 和 Notum）。在生长阶段，DP 中的 Wnt 激动剂和拮抗剂的水平分别逐渐降低和升高。结果，上皮祖细胞中的 Wnt 信号活性降低，导致退行期的诱导。值得注意的是，DP 的特性允许 DP 中的 Wnt 活性持续存在，尽管存在 Wnt 抑制环境，从而同步退行期的诱导和进展。这项研究为信号转导相互作用在连接祖细胞及其龛位以调节组织生长方面的重要性提供了深入了解。
