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bioRxiv · 10.1101/230771

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

Calvo Sanchez, M. I.·Carrasco, E.·Fernandez-Martos, S.·Moreno-Bueno, G.·Bernabeu, C.·Quintanilla, M.·Espada, J.
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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/{beta}-catenin signalling, while regression and resting phases are mainly regulated by Tgf-{beta}/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 coreceptor for members of the Tgf-{beta}/Bmp family of growth factors.\n\nUsing 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 {beta}-catenin binds to the Eng promoter depending on Bmp signalling. Moreover, we show that {beta}-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 crosstalk between Wnt/{beta}-catenin and Bmp/Smad signals.

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Calvo Sanchez, M. I., Carrasco, E., Fernandez-Martos, S., Moreno-Bueno, G., Bernabeu, C., Quintanilla, M., Espada, J.. 2017-12-07. A role for the Tgf-β/Bmp co-receptor Endoglin in the molecular oscillator that regulates the hair follicle cycle. https://doi.org/10.1101/230771

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