A role for the Tgf-β/Bmp co-receptor Endoglin in the molecular oscillator that regulates the hair follicle cycle.
Animals
Bone Morphogenetic Proteins
/ metabolism
Endoglin
/ antagonists & inhibitors
Hair Follicle
/ physiology
Haploinsufficiency
Mice
Mice, Inbred C57BL
Models, Animal
Mouse Embryonic Stem Cells
/ cytology
Promoter Regions, Genetic
Protein Binding
RNA Interference
RNA, Small Interfering
/ metabolism
Signal Transduction
Skin
/ metabolism
Smad Proteins
/ metabolism
beta Catenin
/ chemistry
Journal
Journal of molecular cell biology
ISSN: 1759-4685
Titre abrégé: J Mol Cell Biol
Pays: United States
ID NLM: 101503669
Informations de publication
Date de publication:
01 01 2019
01 01 2019
Historique:
received:
21
02
2018
accepted:
18
09
2018
pubmed:
22
9
2018
medline:
17
6
2020
entrez:
22
9
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30239775
pii: 5101434
doi: 10.1093/jmcb/mjy051
pmc: PMC6359924
doi:
Substances chimiques
Bone Morphogenetic Proteins
0
Endoglin
0
RNA, Small Interfering
0
Smad Proteins
0
beta Catenin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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