title: Snail/Slug-YAP/TAZ complexes cooperatively regulate mesenchymal stem cell function and bone formation.
abstract: Snail and Slug are zinc-finger transcription factors that play key roles in directing the epithelial-mesenchymal transition (EMT) programs associated with normal development as well as disease progression. More recent work suggests that these EMT-associated transcription factors also modulate the function of both embryonic and adult stem cells. Interestingly, YAP and TAZ, the co-transcriptional effectors of the Hippo pathway, likewise play an important role in stem cell self-renewal and lineage commitment. While direct intersections between the Snail/Slug and Hippo pathways have not been described previously, we recently described an unexpected cooperative interaction between Snail/Slug and YAP/TAZ that controls the self-renewal and differentiation properties of bone marrow-derived mesenchymal stem cells (MSCs), a cell population critical to bone development. Additional studies revealed that both Snail and Slug are able to form binary complexes with either YAP or TAZ that, together, control YAP/TAZ transcriptional activity and function throughout mouse development. Given the more recent observations that MSC-like cell populations are found in association throughout the vasculature where they participate in tissue regeneration, fibrosis and cancer, the Snail/Slug-YAP/TAZ axis is well-positioned to regulate global stem cell function in health and disease.
authors.affiliation: a Division of Molecular Medicine and Genetics, Department of Internal Medicine , University of Michigan , Ann Arbor , MI , USA.|b Life Sciences Institute, University of Michigan , Ann Arbor , MI , USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: a Division of Molecular Medicine and Genetics, Department of Internal Medicine , University of Michigan , Ann Arbor , MI , USA.|b Life Sciences Institute, University of Michigan , Ann Arbor , MI , USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Weiss
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000375:Aging / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D002469:Cell Separation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D010012:Osteogenesis; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D046912:Multiprotein Complexes; D010750:Phosphoproteins; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D015534:Trans-Activators; C517794:Wwtr1 protein, mouse; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse
keywords: Hippo; RUNX2; Slug; Snail; TAZ; TEAD; YAP; mesenchymal stem cells; skeletal stem cells