Skin cells undergo asynthetic fission to expand body surfaces in zebrafish

As an animal’s surface area expands during development, skin cell populations must quickly respond to maintain sufficient epithelial coverage. Despite much progress in understanding of skin cell behaviours in vivo1,2, it remains unclear how cells collectively act to satisfy coverage demands at an organismic level. Here we created a multicolour cell membrane tagging system, palmskin, to monitor the entire population of superficial epithelial cells (SECs) in developing zebrafish larvae. Using time-lapse imaging, we found that many SECs readily divide on the animal body surface; during a specific developmental window, a single SEC can produce a maximum of four progeny cells over its lifetime on the surface of the animal. Remarkably, EdU assays, DNA staining and hydroxyurea treatment showed that these terminally differentiated skin cells continue splitting despite an absence of DNA replication, causing up to 50% of SECs to exhibit reduced genome size. On the basis of a simple mathematical model and quantitative analyses of cell volumes and apical surface areas, we propose that ‘asynthetic fission’ is used as an efficient mechanism for expanding epithelial coverage during rapid growth. Furthermore, global or local manipulation of body surface growth affects the extent and mode of SEC division, presumably through tension-mediated activation of stretch-activated ion channels. We speculate that this frugal yet flexible mode of cell proliferation might also occur in contexts other than zebrafish skin expansion.