Abstract
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.
Highlights
Tissue growth in the adult is an orchestrated process that often requires biological clocks to time stem cell and progenitor activity
We show that Fgf and Wnt signaling pathways interact in the dermal papilla (DP) to regulate the hair cycle clock by orchestrating the expression of Wnt agonists (Rspondins) and antagonists (Dkk[2] and Notum)
To unravel the role of Fgf signaling in the DP, we first determined which Fgf receptors mediate Fgf signaling in the DP
Summary
Tissue growth in the adult is an orchestrated process that often requires biological clocks to time stem cell and progenitor activity. Ablation of beta-catenin in the matrix or DP during mid anagen results in premature induction of catagen[25,26] While this clearly illustrates that Wnt signaling activity is required in both the matrix and DP to maintain the anagen phase, it remains unclear whether activation of the Wnt signaling pathway in both compartments converges into a single biological process that regulates the duration of anagen, or Wnt signaling transduction in the matrix and DP independently retain the anagen-maintaining activity of each compartment. Forced expression of the constitutive active form of beta-catenin in the DP does not alter the hair cycle[27] This suggests that while Wnt signaling activity in the DP is required to sustain anagen, it is not sufficient to counteract the catagen-inducing signals. We show that Fgf and Wnt signaling pathways interact in the DP to regulate the hair cycle clock by orchestrating the expression of Wnt agonists (Rspondins) and antagonists (Dkk[2] and Notum)
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