Fig. 2.

Il-11 signaling is essential for scar-free regeneration.

(A) Illustration of zebrafish Il-6 family cytokines and receptors and the downstream signaling pathways. (B) Heatmap showing RT-qPCR analysis of Il-6 family cytokine gene mRNA levels at 1 hpci (n = 6) compared with 1 hour post sham (hps; n = 5). (C) Illustration of wild-type and predicted mutant proteins and gross morphology of adult zebrafish siblings. (D and E) Bright-field images of larval fin fold regeneration (D) (wt siblings, n = 11; mut, n = 5; 72 hpa) and their corresponding quantification of the total fin fold area (E). (F) Wholemount images of Alizarin Red S stained regenerating adult scales [wt siblings, n = 6; mut, n = 5; 7 days post plucking (dpp)]. (G to I) Wholemount images of cardiac ventricles (G) (wt siblings, n = 5; mut, n = 5; 90 dpci), Acid Fuchsin Orange G (AFOG) staining on cryosections (H), and quantification of the scar area (I). (J to L) Wholemount images of caudal fins (J) [wt, n = 6; mut, n = 6, 14 days post amputation (dpa)], AFOG staining on longitudinal cryosections (K), and quantification of the regenerate area (L). SP, signal peptide; TMD, transmembrane domain; aa, amino acids (C). Data represent means ± SD (E, I, and L). Student’s t tests (E, I, and L). n, ventricles (B and G); n, larvae (D); n, adult zebrafish (F); n, caudal fins (J). Black dashed lines demarcate the injured area (G and H) and amputation plane (D and K); white dashed lines demarcate and white arrowheads point to regenerating scales (F); black arrowheads point to fused hemirays [insets in (J) and (K)]; red arrowheads point to the amputation plane (J). Ct values are listed in table S5. Scale bars, 5 mm (C), 100 μm (D), 500 μm (F), 200 μm (G and H), 1 mm (J), and 50 μm (K).