Fgf and Wnt signaling interaction in the mesenchymal niche regulates the murine hair cycle clock

Sarina Harshuk-Shabso, Hila Dressler, Christof Niehrs, Emil Aamar, David Enshell-Seijffers

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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.

Original languageEnglish
Article number5114
JournalNature Communications
Issue number1
StatePublished - 9 Oct 2020

Bibliographical note

Funding Information:
This research was funded by the USA–Israel Binational Science Foundation (BSF: 2013375), the Israel Science Foundation (ISF: 1304/14), and the “Christians for Israel Chair in Medical Research”. We thank Basem Hijazi for statistical assistance and Hofesh Haruach for technical support.

Publisher Copyright:
© 2020, The Author(s).


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