Snail/Slug binding interactions with YAP/TAZ control skeletal stem cell self-renewal and differentiation

• Published in: Nature cell biology Vol. 18; no. 9; pp. 917 - 929
• Main Authors: Tang, Yi, Feinberg, Tamar, Keller, Evan T., Li, Xiao-Yan, Weiss, Stephen J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-09-2016; Nature Publishing Group
• Subjects: 631/136/142; 631/136/83/2360; 631/532/2118; 631/532/2441; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Bone marrow; Cancer Research; Cell Biology; Cell Cycle Proteins; Cell Differentiation; Cell Self Renewal; Cytological research; Developmental Biology; Experiments; Homeostasis; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Life Sciences; Mice, Transgenic; Phosphoproteins - genetics; Phosphoproteins - metabolism; Physiological aspects; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; Stem Cells; Stem Cells - cytology; Stem Cells - metabolism; Trans-Activators; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional coactivators; United States; Ann Arbor Michigan; United States > US; Michigan
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb3394

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.
Weiss and colleagues report that the EMT transcription factors Snail and Slug control skeletal stem cell self-renewal and differentiation by forming transcriptional complexes with the co-activators YAP and TAZ.