A new tension induction paradigm unravels tissue response and the importance of E-cadherin in the developing epidermis

Abstract

The epidermis, being the outermost epithelial layer in metazoans, experiences multiple external and self-generated mechanical stimuli. The tissue-scale response to these mechanical stresses has been actively studied in the adult stratified epidermis. However, the response of the developing bi-layered epidermis to differential tension and its molecular regulation has remained poorly characterised. Here we report an oil injection based method, which in combination with atomic force microscopy (AFM), allows manipulation as well as estimation of tension in the developing epidermis. Our results show that the injection of mineral oil into the brain ventricle of developing zebrafish embryos stretches the overlying epidermis. The epidermal tension increases linearly with the injected volume of oil and the injection of 14-17 nL oil results in a two-fold increase in epidermal tension. This increase in epidermal tension is sufficient to elicit a physiological response characterised by temporal changes in the cell cross-sectional area and an increase in cell proliferation. Our data further indicate that the depletion of E-cadherin in the epidermis is detrimental for tissue integrity under increased mechanical stress. The application of this experimental paradigm in a genetically tractable organism such as zebrafish can be useful in uncovering mechanisms of tension sustenance in the developing epidermis.