Fig. 1: Sympathetic remodeling in metaplastic pancreatic lesions requires DCC.

a Schematic of pancreatic ductal adenocarcinoma (PDAC) progression. Acinar cells undergo acinar-to-ductal metaplasia (ADM) during injury or inflammation, marked by Sox9 or Cytokeratin (CK) 19 expression. While ADM is reversible, oncogenic Kras mutations (e.g., G12D) drive its progression to pancreatic intraepithelial neoplasia (PanIN), a precancerous stage with varying degrees of neoplasia, from low to high-grade carcinoma in situ. b Protocol for ADM induction. Mice received 8 hourly cerulein injections per treatment day. Samples were collected 2 days after the final injection. c, d Immunohistochemistry (IHC) for TH (sympathetic neurons) and F4/80 (macrophages) in healthy and cerulein-treated pancreas. Metaplastic lesions are marked by Sox9. Scale bars: 50 µm; insets, 10 µm. e Quantification of TH⁺ axon density in healthy pancreas (H), metaplastic lesions (M), and adjacent tissue (A) from cerulein-treated mice (Cer). Data: mean ± SEM. n = 6 mice/group; 36 (H), 31 (A), 44 (M) ROIs analyzed. One-way ANOVA. f, g IHC for TH and DCC in healthy and cerulein-treated pancreas. Scale bar: 20 µm. h Quantification of TH⁺ axons co-expressing DCC in healthy (H) and cerulein-treated (Cer) pancreas. Data: mean ± SEM. n  =  3 mice/group; 20 sections analyzed per group. Unpaired t-test, two-tailed. i, j RNAscope for Th and Dcc mRNA in celiac superior mesenteric ganglia (CSMG) of healthy and cerulein-treated mice. Scale bars: 20 µm; insets, 5 µm. k Quantification of Dcc mRNA in CSMG neurons from healthy (H) and cerulein-treated (Cer) mice. Data: mean ± SEM. n  =  3 mice/group; 9 (H) and 8 (Cer) sections analyzed. Unpaired t-test, two-tailed. l Experimental design for tamoxifen injection and cerulein treatment in Th-CreERT2; Dcc^lox/lox mice and Cre-negative controls. m, n IHC for TH and Sox9 in metaplastic lesions (m’, n’) and adjacent tissue (m, n) from cerulein-treated control and Th-CreERT2; Dcc^lox/lox mice. Scale bar: 25 µm. o Quantification of TH⁺ axon density in metaplastic lesions (M) and adjacent tissues (A) in cerulein-treated control (ctr) and Th-CreERT2; Dcc^lox/lox (cKO) mice. Data: mean ± SEM. n  =  3 mice/group; 21 (ctr, M), 11 (ctr, A), 23 (cKO, M), 12 (cKO, A) ROIs analyzed. One-way ANOVA. p-values are indicated in the figure (ns: p > 0.05). Source data are provided as a Source Data file.