Dean, H. C.; Saraswathy, V.; Saini, A.; Ou, T.; McAdow, J.; Tendolkar, A.; Mokalled, M.; Johnson, A. N.

Regenerative capacity varies between tissues, species, and stages of the life cycle. What is less appreciated is that regenerative capacity also varies with the magnitude of the injury, even within a single tissue. Vertebrate skeletal muscle efficiently regenerates following minor injuries; how-ever, extensive injuries may result in incomplete repair, which can be debilitating. To understand if small- and large-scale muscle injuries activate distinct regenerative programs, we developed a systemic muscle injury model in zebrafish. Transcriptomic analysis of muscle and non-muscle tissues revealed that systemic and local muscle injuries elicit distinct molecular responses, both quantitatively and qualitatively. Systemic muscle injury activated the expression of Heparin bind-ing epidermal-like growth factor (Hb-EGF) in the epidermis, and Hb-EGF is necessary for sys-temic muscle repair. Conversely, local muscle injury did not induce Hb-EGF expression and Hb-EGF was not required for local muscle repair. These studies suggest that large- and small-scale muscle injuries activate different regenerative programs, resulting in either systemic or local re-pair.