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

ABSTRACT: 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/?-catenin signalling, while regression and resting phases are mainly regulated by Tgf-?/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-?/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 ?-catenin binds to the Eng promoter depending on Bmp signalling. Moreover, we show that ?-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/?-catenin and Bmp/Smad signals.

SUBMITTER: Calvo-Sanchez MI 

PROVIDER: S-EPMC6359924 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature