title: Snail/Slug binding interactions with YAP/TAZ control skeletal stem cell self-renewal and differentiation.
abstract: Bone-marrow-derived skeletal stem/stromal cell (SSC) self-renewal and function are critical to skeletal development, homeostasis and repair. Nevertheless, the mechanisms controlling SSC behaviour, particularly bone formation, remain ill-defined. Using knockout mouse models that target the zinc-finger transcription factors Snail or Slug, or Snail and Slug combined, a regulatory axis has been uncovered wherein Snail and Slug cooperatively control SSC self-renewal, osteoblastogenesis and bone formation. Mechanistically, Snail/Slug regulate SSC function by forming complexes with the transcriptional co-activators YAP and TAZ in tandem with the inhibition of the Hippo-pathway-dependent regulation of YAP/TAZ signalling cascades. In turn, the Snail/Slug-YAP/TAZ axis activates a series of YAP/TAZ/TEAD and Runx2 downstream targets that control SSC homeostasis and osteogenesis. Together, these results demonstrate that SSCs mobilize Snail/Slug-YAP/TAZ complexes to control stem cell function.
authors.affiliation: Division of Molecular Medicine &Genetics, Department of Internal Medicine and the Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Division of Molecular Medicine &Genetics, Department of Internal Medicine and the Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Tamar
authors.initials: T
authors.lastname: Feinberg
authors.affiliation: Department of Pathology, Department of Urology and the Institute of Gerontology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Evan T
authors.initials: ET
authors.lastname: Keller
authors.affiliation: Division of Molecular Medicine &Genetics, Department of Internal Medicine and the Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Li
authors.affiliation: Division of Molecular Medicine &Genetics, Department of Internal Medicine and the Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Weiss
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D000066673:Cell Self Renewal; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; C517794:Wwtr1 protein, mouse; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse