Extended Data Fig. 6: Neuron-specific Sarm1 inactivation delays tumour development.

a, Schematic showing intraventricular injection of AAV8-Syn-EGFP (GFP) or AAV8-Syn-SARM1-CDN-EGFP (SarmDN) alongside npp tumour inducing plasmids at P2. b, Representative images of the injury site in npp tumour-bearing brains transduced with GFP or SarmDN AAVs at P2 and subjected to axonal transection at intermediate disease stage. Tissue was stained for neurofilament (grey). GFP (green) denotes successful neuronal transduction. Note axonal protection in the SarmDN-transduced brains. Scale bar=200 μm. GFP n = 3, SarmDN n = 3 mice. c, Representative images of tdTomato (red) and GFP (green) fluorescence in npp tumours injected intraventricularly with GFP or SarmDN AAVs at the time of tumour induction (P2), subjected to Sham (left panel) or Injury (right panel) at intermediate stage and stained for EdU (grey) and DAPI (blue). Scale bar=200 μm. GFP Sham n = 5, GFP Injury n = 5, SarmDN Sham n = 4, SarmDN Injury n = 5 mice. d, Quantification of the percentage of proliferating EdU⁺/tdTomato⁺ tumour cells over total number of tdTomato⁺ tumour cells in tumours from c. Mean ± SEM. Multiple two-sided unpaired t tests. GFP Sham n = 5, GFP Injury n = 5, SarmDN Sham n = 4, SarmDN Injury n = 5 mice. p = 0.0411 (GFP injected, sham vs injury (excluding injury site); p = 0.0309 (GFP injected, Injury (excluding injury site) vs Injury (injury site), p = 0.0043 (GFP Injury (excluding injury site) vs SarmDN Injury (excluding injury site). e-f, Quantification of GFAP area (e) and CD68 intensity (IntDen, f) within the tdTomato region in tumours from c; injury site and the rest of the tumour area were quantified separately and normalized to Sham in each genotype. Mean ± SEM. Multiple two-sided unpaired t tests. GFP Sham n = 7, GFP Injury n = 5, SarmDN Sham n = 4, SarmDN Injury n = 5 mice. In e, p = 0.02 (GFP injected, Sham vs Injury (excluding injury site); p = 0.0012 (GFP injected, Sham vs Injury (injury site). g, Schematic showing intratumoural injection of AAV8-Syn-EGFP (GFP) or AAV8-Syn-SARM1-CDN-EGFP (SarmDN) at intermediate/late time point. h, Representative images of tdTomato (red) and GFP (green) fluorescence in WT npp tumours injected intratumorally with GFP or SarmDN AAVs at intermediate disease stage and stained for EdU (grey). Scale bar=200 μm. Images are representative of 4 mice per condition. i, Quantification of percentage EdU⁺/tdTomato⁺ tumour cells over total number of tdTomato⁺ tumour cells in tumours from h. Mean ± SEM. Two-sided unpaired t test. GFP n = 4, SarmDN n = 4 mice. p = 0.0248 j, as in h for tumours injected with AAVs at late stage. Scale bar=200 μm. Images are representative of 5 GFP mice and 4 SarmDN mice. k, Quantification of percentage EdU⁺/tdTomato⁺ tumour cells over total number of tdTomato⁺ tumour cells in tumours from j. Mean ± SEM. Two-sided unpaired t test. GFP n = 5, SarmDN n = 4 mice.

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