Fig. 3

The role of Notch and Wnt signaling in bone or zebrafish fin regeneration. a Upon bone injury, the bone marrow mesenchymal stem cells (MSCs) give rise to osteoblasts, which terminally differentiate into osteocytes for bone repair. The osteoblasts, the bone-forming cells, cooperate with the multinucleated osteoclasts, the bone-resorbing cells, to control the bone remodeling. The canonical Wnt/β-catenin signaling enhances bone healing through accelerating MSC differentiation into osteoblasts and chondrocytes, which form cartilage. In contrast, Notch signaling in MSCs functions to inhibit their differentiation through Hes1-mediated suppression of Wnt signaling. In osteocytes, activation of Notch signaling promotes bone formation by inhibiting the expressions of Wnt-inhibitor Sost and Dkk1. In osteoclasts, Notch signaling is required for bone resorption. b During zebrafish tail fin regeneration, a mass of undifferentiated proliferating mesenchymal progenitor-like cells at the amputation plane form the blastema, which gives rise to all the cell types that form the new fin. Notch signaling in proximal blastema functions to maintain blastema cells in an undifferentiated and proliferative state and block osteoblast differentiation. Wnt signaling is required for the blastema formation and subsequent proliferation. Wnt signaling is active in non-proliferative distal blastema and functions upstream of Notch signal to regulate blastema cell proliferation