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Citrullination regulates wound responses and tissue regeneration in zebrafish

Authors: 
Golenberg N, Squirrell JM, Bennin DA, Rindy J, Pistono PE, Eliceiri KW, Shelef MA, Kang J, Huttenlocher A
Citation: 
bioRxiv. 2019:[preprint] doi:10.1101/2019.12.27.889378
Abstract: 
Calcium signaling is an important early step in wound healing, yet how these early signals promote regeneration remains unclear. Peptidylarginine deiminases (PADs), a family of calcium-dependent enzymes, catalyze citrullination, a post-translational modification that alters protein function and has been implicated in autoimmune diseases. We generated a mutation in the single zebrafish ancestral pad gene, padi2, resulting in a loss of detectable calcium-dependent citrullination. The padi2 mutants exhibit impaired resolution of inflammation and regeneration after caudal fin transection. Further, we identified a new subpopulation of cells displaying citrullinated histones within the notochord bead following tissue injury. Citrullination of histones in this region was absent and wound-induced proliferation was perturbed in Padi2-deficient larvae. Taken together, our results show that Padi2 is required for the citrullination of histones within a group of cells in the notochord bead, and for promoting wound-induced proliferation required for efficient regeneration. These findings identify Padi2 as a potential intermediary between early calcium signaling and subsequent tissue regeneration.
Epub: 
Not Epub
Organism or Cell Type: 
zebrafish
Delivery Method: 
microinjection