YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate

Antonio Totaro, Martina Castellan, Giusy Battilana, Francesca Zanconato, Luca Azzolin, Stefano Giulitti, Michelangelo Cordenonsi and Stefano Piccolo ()
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Antonio Totaro: University of Padua School of Medicine
Martina Castellan: University of Padua School of Medicine
Giusy Battilana: University of Padua School of Medicine
Francesca Zanconato: University of Padua School of Medicine
Luca Azzolin: University of Padua School of Medicine
Stefano Giulitti: University of Padua School of Medicine
Michelangelo Cordenonsi: University of Padua School of Medicine
Stefano Piccolo: University of Padua School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract How the behaviour of somatic stem cells (SCs) is influenced by mechanical signals remains a black-box in cell biology. Here we show that YAP/TAZ regulation by cell shape and rigidity of the extracellular matrix (ECM) dictates a pivotal SC decision: to remain undifferentiated and grow, or to activate a terminal differentiation programme. Notably, mechano-activation of YAP/TAZ promotes epidermal stemness by inhibition of Notch signalling, a key factor for epidermal differentiation. Conversely, YAP/TAZ inhibition by low mechanical forces induces Notch signalling and loss of SC traits. As such, mechano-dependent regulation of YAP/TAZ reflects into mechano-dependent regulation of Notch signalling. Mechanistically, at least in part, this is mediated by YAP/TAZ binding to distant enhancers activating the expression of Delta-like ligands, serving as ‘in cis’ inhibitors of Notch. Thus YAP/TAZ mechanotransduction integrates with cell–cell communication pathways for fine-grained orchestration of SC decisions.

Date: 2017
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DOI: 10.1038/ncomms15206

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