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.
Keywords: Hippo; RUNX2; Slug; Snail; TAZ; TEAD; YAP; mesenchymal stem cells; skeletal stem cells.