Wnt signalling and its importance in hair follicle development and differentiation has been largely described at the individual cell or hair follicle level. We aimed to generate a model for in vivo quantitative monitoring of beta catenin activity in the skin to follow wnt signalling in mouse back skin at the macroscopic level.
We generated mice harbouring a luciferase reporter gene under the control of beta catenin binding sites TCF/LEF inducible promoter. Using in vivo bioluminescence imaging, we were able to track beta catenin activity in the skin from P1 in rostro-caudal waves. The signal peaked at P9 with >400 fold increase. Histological assessment allowed attributing signal levels to specific phases of the hair follicle cycle. Furthermore, we were able to reproduce all macroscopic features of hair follicle biology, such as propagating waves, border stability, refractory telogen and random initiation points. In adults, hair plucking or cyclosporine predictably induced beta catenin activity with an intense signal appearing 6 days after initiation.
We took advantage of the possibilities offered by this model to assess the level of beta-catenin activity in situations of health and disease. During pregnancy, the peak of beta-catenin activity was not modified. However, there was a delay in the natural entry into anagen. Similarly wound healing and models of defective hair growth affected the level of bioluminescence. Finally, mathematical modelling of beta-catenin signalling based on a generic dynamical mechanism for producing oscillatory behavior in activator-inhibitor system allowed to reproduce the characteristic patterns of hair follicle progression and cycling in a two dimensional grid.
In conclusion, tracking Wnt signalling macroscopically in the mouse back skin allows a detailed understanding of hair cycle progression and could be used for screening drugs or molecular targets.