Epidermal threads reveal the origin of hagfish slime

Fiber-reinforced soft materials possess high flexibility with high strength but are rare in nature. Hagfishes can produce a tough, fibrous slime within a fraction of a second by ejecting two cellular products, mucus and threads, into seawater. With thousands of silk-like threads, the slime is highly effective in defending against large predators. However, the evolutionary origin of hagfish slime remains unresolved, with the presence of another, putatively homologous thread in the epidermis providing circumstantial evidence for an epidermal origin. Here, we investigated the epidermal threads produced in hagfish skin. We found that these threads average ∼2 mm in length and ∼0.5 μm in diameter, or ∼80 times shorter and ∼4 times thinner than the slime threads, characterizing the second longest intracellular fiber. The entire hagfish body is covered by a dense layer of epidermal thread cells, with each square millimeter of skin storing a total of ∼96 cm threads. Experimentally induced damage to a hagfish’s skin caused the release of threads, which together with mucus, formed an adhesive epidermal slime that is more fibrous and less dilute than the defensive slime. Transcriptome analyses further revealed that the epidermal threads are ancestral to the slime threads, with duplication and diversification of thread genes in parallel with the evolution of slime glands. These results support an epidermal origin of hagfish slime and slime glands, as driven by predator selection for stronger and more voluminous slime. ### Competing Interest Statement The authors have declared no competing interest.