(A) Hagfish defensive slime is produced by rapid ejection and rupture of mucous cells and thread cells into seawater by slime glands. Top shows a schematic sequence of slime formation. Threads and mucus are released from ruptured cells and mix with seawater to form large volumes of dilute, soft, viscoelastic slime (lower right). (B) A consensus tree of chordates highlighting the origins of epidermal thread cells and hagfish slime glands. Orthologs of intermediate filament thread genes are expressed in the skin of lampreys, hagfishes, teleost fishes, and amphibians (orange shade), and thus likely have an origin that dates back to the common ancestor of vertebrates. Epidermal cells producing large threads are only known in hagfishes and lampreys (see also Figure 1—figure supplement 1), and thus epidermal thread cells likely originated in their common ancestor. The gray segment highlights a wide window of time between 138 and 310 million years ago when the hagfish slime glands evolved (Miyashita, 2020).