Investigating Dynamics of Tissue Regeneration via Live Imaging of Zebrafish Scales

Abstract

Regeneration occurs throughout the animal kingdom and is a well-studied feature of many model organisms, yet the field lacks a fundamental understanding of the real-time dynamics of cell behavior during regeneration. I discuss how existing knowledge of regeneration may be used to inform efforts to translate these remarkable feats of animals to human regeneration and present research that uses live imaging to improve understanding of cell origins and diversification during regeneration in the scale, focusing specifically on osteoblasts the matrix-depositing cells that divide and heal bone injuries. I developed an imaging platform to monitor and quantify individual and collective behaviors of osteoblasts in adult zebrafish scales. I show that a founder pool of osteoblasts emerges through de novo differentiation within one day of scale plucking, then diversifies across the primordium by two days after injury, with region-specific changes in proliferation, cell shape, and cell death rates coincident with acquisition of mature scale morphology. I also demonstrate a role for Fgf signaling in scale regeneration and present tools for high resolution imaging studies of basal epidermal cells during skin and scale injury. These findings demonstrate the value of live imaging in revealing novel biology and gaining a more complete picture of the many complex processes that must be elegantly choreographed to achieve tissue regeneration.