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

作     者：Maria I.Calvo-Sanchez Sandra Fernandez-Martos Elisa Carrasco Gema Moreno-Bueno Carmelo Bernabeu Miguel Quintanilla Jesus Espada 

作者机构：Instituto de Investigaciones Biomedicas'Alberto Sols'Consejo Superior de Investigaciones Cientificas(CSIC)-Departamento de BioqufmicaUniversidad Autonoma de Madrid(UAM)Madrid 28029Spain Instituto de Investigaciones BiosanitariasFacultad de Ciencias ExperimentalesUniversidad Francisco de Vitoria(UFV)Pozuelo de Alarcon 28223Spain Centro de Investigacion Biomedica en Red de Cancer(CIBERONC)Spain Centro de Investigaciones BiologicasConsejo Superior de Investigaciones Cientificas(CSIC)and Centro de Investigacion Biomedica en Red de Enfermedades Raras(CIBERER)Madrid 28040Spain Centro Integrativo de Biologfa y Quimica AplicadaUniversidad Bernardo O'HigginsSantiago 8370854Chile Instituto Ramon y Cajal de Investigacion Sanitaria(IRYCIS)Hospital Universitario Ramon y CajalMadridSpain 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2019年第11卷第1期

页      面：39-52页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 07[理学] 071009[理学-细胞生物学] 

基　　金：supported by grants from Ministerio de Economia y Competitividad of Spain Comunidad de Madrid Instituto de Salud Carlos III Centro de Investigacion Biomedica en Red de Enfermedades Raras financed jointly by the European Regional Development Funds((FEDER). E.C.and M.I.C.) supported by Spanish MECD-FPU and UAM-FPI fellowships, respectively 

主　　题：Endoglin hair follicle skin stem cells Wnt/β-catenin Tgf-β/Bmp/Smad 

摘      要：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 thatβ-catenin binds to the Eng promoter depending on Bmp signalling.Moreover,we show thatβ-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.