Transgenic flash mice for in vivo quantitative monitoring of canonical Wnt signaling to track hair follicle cycle dynamics

J Invest Dermatol. 2014 Jun;134(6):1519-1526. doi: 10.1038/jid.2014.92. Epub 2014 Feb 14.

Abstract

Hair follicles (HFs) upon development enter a lifelong cycle of growth, regression, and resting. These phases have been extensively studied at the cellular and molecular levels for individual HFs. However, HFs group into domains with coordinated cycling strongly influenced by their environment. These macroscopic hair domains have been difficult to study and can be influenced by physiological or pathological conditions, such as pregnancy or skin wounds. To robustly address this issue, we generated a mouse model for quantitative monitoring of β-catenin activity reflecting HF cycle dynamics macroscopically by using live bioluminescence imaging. These mice allowed live tracking of HF cycles and development, and highlighted hair regenerative patterns known to occur through macro-environmental cues, including initiation events, propagating anagen and border stability, and allowed refinement of a mechanistic mathematical model that integrates epidermal cell population dynamics into an excitable reaction-diffusion model. HF cycling could be studied in situations of pregnancy, wound healing, hair plucking, as well as in response to cyclosporine or Wnt3a stimulation. In conclusion, we developed a model for analysis of HF cycling at the macroscopic level that will allow refined analysis of hair cycle kinetics as well as its propagation dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclosporine / chemistry
  • Female
  • Genes, Reporter
  • Hair / embryology*
  • Hair / physiology
  • Hair Follicle / growth & development*
  • Hair Follicle / metabolism
  • Luciferases, Firefly / genetics
  • Luminescence
  • Mice
  • Mice, Transgenic
  • Models, Theoretical
  • Pregnancy
  • Transgenes
  • Wnt Signaling Pathway*
  • Wnt3A Protein / metabolism
  • Wound Healing
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, mouse
  • Wnt3A Protein
  • Wnt3a protein, mouse
  • beta Catenin
  • Cyclosporine
  • Luciferases, Firefly