Common and Distinctive Functions of the Hippo Effectors Taz and Yap In
TISSUE-SPECIFIC STEM CELLS aRandall Division of Cell and Common and Distinctive Functions of the Hippo Molecular Biophysics, King’s College London, London, UK; Effectors Taz and Yap in Skeletal Muscle Stem Cell bSchool of Medicine, Medical Sciences & Nutrition, Function University of Aberdeen, Foresterhill, Aberdeen, a b b a Scotland, UK; cSystems CONGSHAN SUN, VANESSA DE MELLO, ABDALLA MOHAMED, HUASCAR P. O RTUSTE QUIROGA, c b d,e,f Biology Ireland, Conway AMAYA GARCIA-MUNOZ, ABDULLAH AL BLOSHI, ANNIE M. TREMBLAY, c g b c Institute, Dublin, Ireland; ALEXANDER VON KRIEGSHEIM, ELAINA COLLIE-DUGUID, NEIL VARGESSON, DAVID MATALLANAS, d b,h a Stem Cell Program, HENNING WACKERHAGE, PETER S. ZAMMIT Children’s Hospital, Boston, Massachusetts, USA; Key Words. Taz • Yap • Tead • Satellite cells • Muscle stem cells eDepartment of Stem Cell and Regenerative Biology, Harvard University, ABSTRACT Cambridge, Massachusetts, USA; fHarvard Stem Cell Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regen- Institute, Cambridge, eration, regulating gene expression especially via Tead transcription factors. To investigate their Massachusetts, USA; gCentre role in skeletal muscle stem cells, we analyzed Taz in vivo and ex vivo in comparison with Yap. for Genome Enabled Biology Small interfering RNA knockdown or retroviral-mediated expression of wild-type human or con- and Medicine, School of stitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a func- Medicine, Medical Sciences tion shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic and Nutrition, University of differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while mus- Aberdeen, Foresterhill, cle growth was mildly affected in Taz (gene Wwtr1–/–) knockout mice, there were no overt Aberdeen, Scotland, UK; effects on regeneration.
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