Unfolding the hair cycle clock

The hair follicle, which cycles between growth and regression in a timely-restricted mode, is an excellent model system to unravel the molecular mechanisms underlying biological clocks. While numerous models and theories have been proposed during the last five decades to explain the cyclic nature of the hair follicle, the biological clock that dictates the periodicity of the hair cycle remains poorly understood. We have recently revealed that the crosstalk between Fgf and Wnt signaling pathways in the mesenchymal niche of the hair follicle, the DP, generates adjustable positive and negative feedback loops that molecularly couple the epithelial and mesenchymal compartments in order to regulate the duration of the growth phase. Furthermore, the distinct properties of matrix and DP cells uncouple Wnt activity in the DP from Wnt activity in the matrix and thus allow the synchronous induction of the regression phase. By further genetically manipulating the molecular clock in the DP, we are now able to arrest the follicles in an active state of growth as shown in the image on the left. We aim to unravel the components of the hair cycle clock and to understand the mechanism by which this biological clock orchestrates the hair cycle.