Fig. 3: Netrin-1 promotes the innervation of precancerous PanIN lesions.

a–c IHC for Netrin-1 and Sox9 in asymptomatic tissue (a), PanIN lesion (b), and PDAC tumor from 6.5-week-old KIC mice. Scale bar: 50 µm. d Quantification of Netrin-1 fluorescence in adjacent tissue (A), PanIN lesions (P), and PDAC tumors (T). Data: mean ± SEM. n  =  3 mice, 16 (A), 15 (P), 16 (T) ROIs analyzed. One-way ANOVA. e, f RNAscope for Th and Dcc mRNA in celiac superior mesenteric ganglia (CSMG) from 6.5-week-old control (e) and KIC (f) mice. Scale bars: 20 µm; insets, 5 µm. g Quantification of Dcc mRNA in CSMG neurons from control (ctr) and KIC mice. Data: mean ± SEM. n  = 3 mice/group; 5 (ctr) and 6 (KIC) sections analyzed. Unpaired t-test, two-tailed. h Schematic of the experimental design for antibody treatment of KIC mice. i–l left panels: 3D maximum intensity projections of TH⁺ axons in PanIN lesions and adjacent tissues from isotype (i) or anti-Netrin-1-treated (k) KIC mice. Right panels: 2D optical sections of PanIN lesions identified by tissue autofluorescence (AF). j, l show reconstructed TH⁺ axons and branching points (purple). Scale bars: 100 µm (i, k, left panels of j and l), 20 µm (right panels of j, l). m, n TH⁺ axon density (m) and branching (n) in PanIN lesions (P) and adjacent tissues (A) following anti-Netrin-1 (αNet) or isotype (Iso) treatment. Data: mean ± SEM. n  =  3 mice/group; 9 ROIs analyzed per group. One-way ANOVA. p-values are indicated in the figure (ns: p > 0.05). Source data are provided as a Source Data file.