Osmolarity-independent electrical cues guide rapid response to injury in zebrafish epidermis
Preprint posted on August 05, 2020 https://www.biorxiv.org/content/10.1101/2020.08.05.237792v1
Article now published in eLife at http://dx.doi.org/10.7554/elife.62386
Epithelial tissue can act as a strong resistance barrier by minimizing the passive flow of ions down the concentration gradients that maintain trans-epithelial potential (TEP). This can generate a significant electrical field around the tissue. Wounding or injury in the epithelial tissue can cause electric flow currents in the direction of the injury, which can be maintained for a long time. This regulates the wound response by guiding cells to migrate and cover the wound (Reid and Zhao, 2014). Cell migration in response to the electrical field has been hypothesized to be controlled by actin alignment, reorganization, and distribution of plasma membrane proteins and organelles (Robinson KR. 1985). But what are the electrical cues in-vivo that guide cell polarization and migration during a wound response? In this preprint, the authors test the role of osmolarity, tonicity and the electrical field in the wound response.
- Tissue laceration in zebrafish tail leads to tissue contraction and induces a migratory response which is concomitant with calcium spikes at different rates in the first few minutes of the injury.
- Injury leads to actin polarization with the formation of actin-rich ruffles different from isolated keratocytes.
- This polarization was evident up to several hundred micrometers away from the laceration.
- Osmolarity- Cell speed was strongly reduced in sodium chloride solution compared to other isosmotic solutions, which suggested that wound-induced cell migration depends on the local sodium-chloride ionic activity, not just the osmotic effect. Cells largely lacked polarization and actin reorganization in sodium chloride isosmotic solution.
- Tonicity-Authors show that cell migration and wound response is independent of the tonicity of the isosmotic solutions (identical concentration of different salts inducing water flow).
- Electrical field- One of the cues during injury is the disruption of trans-epithelial potential, which is maintained by sodium and chloride ions across the skin. Authors show that cellular wound response is directional towards the cathode and the cells respond in a polarized fashion towards exogenous wound cues.
What I like about the preprint-
The idea that cells respond to differences in the local electrical field around tissues have been put forward some time ago, but a careful dissection of mechanisms has yet not been achieved. This work focusses on carefully dissecting different hypotheses that would be responsible for polarized cell migration after injury in zebrafish. This work also reinforces the idea that trans-epithelial potential and generation of electrical flows is an important factor to be considered in wound response in-vivo.
Questions to the authors-
- This work shows that trans-epithelial potential (TEP) is important and disruption of TEP can induce cell polarization. It has been suggested that TEP is maintained by ion channels and sodium-potassium pumps. With wounding, electrical flows are generated locally eliciting cellular responses. Could the authors suggest how are these flows maintained over time?
- It has also been shown that cell polarization is evident several hundred microns away from the wound. How is this response elicited when the changes in the electrical flows are so local? Or can small lacerations cause large scale electrical flows?
Robinson KR. The responses of cells to electrical fields: a review. J Cell Biol. 1985;101(6):2023-2027. doi:10.1083/jcb.101.6.2023
Reid B, Zhao M. The Electrical Response to Injury: Molecular Mechanisms and Wound Healing. Adv Wound Care (New Rochelle). 2014;3(2):184-201. doi:10.1089/wound.2013.0442
Posted on: 28th October 2020Read preprint
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