A role for the Tgf-β/Bmp co-receptor Endoglin in the molecular oscillator that regulates the hair follicle cycle

J Mol Cell Biol. 2019 Jan 1;11(1):39-52. doi: 10.1093/jmcb/mjy051.


The hair follicle is a biological oscillator that alternates growth, regression, and rest phases driven by the sequential activation of the proliferation/differentiation programs of resident stem cell populations. The activation of hair follicle stem cell niches and subsequent entry into the growing phase is mainly regulated by Wnt/β-catenin signalling, while regression and resting phases are mainly regulated by Tgf-β/Bmp/Smad activity. A major question still unresolved is the nature of the molecular switch that dictates the coordinated transition between both signalling pathways. Here we have focused on the role of Endoglin (Eng), a key co-receptor for members of the Tgf-β/Bmp family of growth factors. Using an Eng haploinsufficient mouse model, we report that Eng is required to maintain a correct follicle cycling pattern and for an adequate stimulation of hair follicle stem cell niches. We further report that β-catenin binds to the Eng promoter depending on Bmp signalling. Moreover, we show that β-catenin interacts with Smad4 in a Bmp/Eng-dependent context and both proteins act synergistically to activate Eng promoter transcription. These observations point to the existence of a growth/rest switching mechanism in the hair follicle that is based on an Eng-dependent feedback cross-talk between Wnt/β-catenin and Bmp/Smad signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • Endoglin / antagonists & inhibitors
  • Endoglin / genetics
  • Endoglin / metabolism*
  • Hair Follicle / physiology*
  • Haploinsufficiency
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Skin / metabolism
  • Skin / pathology
  • Smad Proteins / metabolism
  • beta Catenin / chemistry
  • beta Catenin / metabolism


  • Bone Morphogenetic Proteins
  • Endoglin
  • RNA, Small Interfering
  • Smad Proteins
  • beta Catenin