Fig. 9. A cellular model of zebrafish fin regeneration. During stage 1 (0-12 hours; wound healing), the wound epidermis is formed by migrating epithelial cells. In stage 2 (12-48 hours; blastema formation), the basal epidermis is formed, mesenchymal tissue proximal to the amputation plane begins to disorganize and intraray mesenchymal cells proliferate and move upward. A subset of early mesenchymal proliferating cells (red) expresses msxb (blue nuclei). A number of msxb-positive proliferating cells continue to increase throughout blastema formation. Just before the onset of regenerative outgrowth, blastemal cells segregate into msxb-positive, non-proliferating DMB and msxb-negative proliferating PZ, with a gradient of proliferation between the two domains. During stage 3 (48 hours 1 week; regenerative outgrowth), the gradient of msxb expression and proliferation is maintained, controlling the direction of outgrowth. Cells in the PZ proliferate vigorously and move in the proximal direction to differentiate. A zone of negative proliferation in the DMB maintains the directionality of the outgrowth by inhibiting proliferation.