Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish.
Tissue injury can lead to scar formation or tissue regeneration. How regenerative animals sense initial tissue injury and transform wound signals into regenerative growth is an unresolved question. Previously, we found that the Src family kinase (SFK) Lyn functions as a redox sensor in leukocytes that detects H(2)O(2) at wounds in zebrafish larvae. In this paper, using zebrafish larval tail fins as a model, we find that wounding rapidly activated SFK and calcium signaling in epithelia. The immediate SFK and calcium signaling in epithelia was important for late epimorphic regeneration of amputated fins. Wound-induced activation of SFKs in epithelia was dependent on injury-generated H(2)O(2). A SFK member, Fynb, was responsible for fin regeneration. This work provides a new link between early wound responses and late regeneration and suggests that redox, SFK, and calcium signaling are immediate "wound signals" that integrate early wound responses and late epimorphic regeneration.
PubMed ID: 23045550
PMC ID: PMC3471241
Article link: J Cell Biol.
Grant support: CA157322 NCI NIH HHS , ES007015 NIEHS NIH HHS , GM074827 NIGMS NIH HHS
Genes referenced: hck itih3 lyn mapk1 spi1 yes1
Article Images: [+] show captions
|Figure 1. Redox and SFK signaling at wounds. (A) Immunofluorescence of pSFK (phosphorylation of SFK activation loop tyrosine) in 3-dpf larvae at various time points. Arrows indicate the position of tail transection. The dotted line is the position of tail transection. (B) Immunofluorescence of pSFK and pErk in 3-dpf larvae at 30 min after tail transection. DPI and PP2 inhibit SFK activation at wounds but not Erk activation. (C) Immunofluorescence of pSFK and Cadherin in 2.5-dpf larvae at 30 min after tail transection. hpw, hour postwounding. Bars, 50 µm.|