PT  - JOURNAL ARTICLE
AU  - Netta Golenberg
AU  - Jayne M. Squirrell
AU  - David A. Bennin
AU  - Julie Rindy
AU  - Paige E. Pistono
AU  - Kevin W. Eliceiri
AU  - Miriam A. Shelef
AU  - Junsu Kang
AU  - Anna Huttenlocher
TI  - Citrullination regulates wound responses and tissue regeneration in zebrafish
AID  - 10.1101/2019.12.27.889378
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 2019.12.27.889378
4099  - http://biorxiv.org/content/early/2019/12/27/2019.12.27.889378.short
4100  - http://biorxiv.org/content/early/2019/12/27/2019.12.27.889378.full
AB  - 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.Summary Golenberg et al. developed a citrullination-deficient zebrafish and demonstrated a role for Padi2 in fin wound responses and regeneration. This work identified a distinct population of cells within the regenerative notochord bead that exhibited wound-induced histone citrullination.