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https://www.nature.com/articles/s41586-020-03085-8
Control of osteoblast regeneration by a train of Erk activity waves. How is tissue growth organized in vertebrate regeneration? To address this question, we turned to the bony regenerating scales of zebrafish: a simple system amenable to live imaging. 1/8
Control of osteoblast regeneration by a train of Erk activity waves. How is tissue growth organized in vertebrate regeneration? To address this question, we turned to the bony regenerating scales of zebrafish: a simple system amenable to live imaging. 1/8
Scales are covered by a layer of bone-forming osteoblasts. After scale loss, a new osteoblast tissue forms in a few days; then, this osteoblast tissue grows by hypertrophy. By tracking tissue movements, we found dynamic rings of tissue expansion (green). 2/8
To examine the signaling basis of expansion rings, we implemented a live sensor of Erk activity in scales and discovered ring-like waves of Erk activity. Erk activity waves originate at a central source and travel from the core to the edge of scales as expanding rings. 3/8
Several waves travel across each scale throughout regeneration. 4/8
Quantitative analysis and perturbations showed that Erk activity propagates as an excitable wave, dependent on Fgf signaling. A simple mathematical model with a positive Fgf <-> Erk and a negative Erk |-> inhibitor feedback loops can explain wave propagation. 5/8
We propose that Erk activity waves are an efficient mechanism to transport information across large tissues, whereas simple diffusion may take long time. What information are Erk waves delivering? 6/8
We discovered that Erk activity waves coordinate tissue growth. Erk activity waves pattern tissue growth in rings of tissue expansion. Throughout regeneration, the number of waves that crossed the tissue determines the extent of tissue growth and final scale size.
7/8
7/8
A favorite experiment: we perturbed wave generation by brief treatment with an Fgfr inhibitor. Erk waves disappeared for ~4 d and growth stalled. When waves re-emerged, growth resumed, with the same extent of growth per wave as in unperturbed regenerating scales. 8/8
Conclusion. We discovered a train of Erk activity waves that propagates from a central source and orchestrates bone tissue growth in zebrafish. We propose that waves of transmitted signals serve as a mechanism of cellular organization within large regenerating tissues.
