Electrical signalling and growth control in zebrafish fin regeneration

ongoing

The existence of endogenous electric fields in tissues is a fundamental feature for successful morphogenesis and repair processes, conserved across species. In a regeneration setting, wound electric currents can last hours to days, even after the wound is closed. Altering such currents by perturbing its underlying ion flows has been shown to affect organ growth via an increase in proliferative rates. Therefore, electric field directly takes part in regeneration. However, the relationship between ion flows, membrane potential, and cell proliferation for driving the regeneration response is not well understood. This project aims to uncover the dynamic electrical environmental changes that cells are exposed to upon organ damage, and how these can be coupled with biochemical signalling towards starting proliferation. By using the regenerating zebrafish larval fin as an experimental model, I will establish quantitative and interdisciplinary approaches that bridges injury sensing and regeneration dynamics across length and time scales. By establishing fast in vivo imaging and electrophysiology assays, I will measure the electrical signals in the fin tissue upon injury, providing an in-depth kinetic analysis of the electric spatiotemporal changes occurring within seconds of injury. In parallel, I will establish an analytic electrohydraulics model that connects cell-based ionic flows to tissue-scale electric field and currents, being continuously interwoven with experimental data and the idea of flexoelectricity. Then, I will generate and engineer optogenetic tools to spatiotemporally perturb ionic flows and electrochemical coupling strengths, directly testing the hypothesis of ion flow-derived electric currents as voltage-gated triggers for cell proliferation. This combined strategy will provide a first-of-the-kind quantitative and mechanistic study in the emerging field of bioelectricity.