Extended Data Fig. 10: Inhibition of the Dll4-Notch2 axis promotes hypertrophic response.

a, Gene expression of Notch ligands (Dll1, Dll4, Jag1, and Jag2) in CD31⁺ ECs and myofibres isolated from overloaded or control PLA muscle (n = 4 mice per condition). qPCR data of ECs and myofibres were normalised to Pecam1 and GAPDH, respectively. b–d, To assess the hypertrophic response of muscle, N2^f/f and N2^–/– mice were overloaded (OL) by tenotomy for 14 days. b, Time course. c,d, Muscle weight (c) and OL-induced weight gain of PLA muscle (d), PLA muscle weight/body weight of OL vs. sedentary control (n = 6-8). e–g, Wild-type mice were intraperitoneally administered with DAPT (10 mg kg⁻¹ body weight) following tenotomy. e, Time course. f,g, Muscle weight (f) and OL-induced PLA weight gain (g) (n = 6). h–j, Effects of EC-specific conditional deletion of Dll4 on muscle hypertrophy. h, Experimental scheme for assessing the hypertrophic response of EC-specific Dll4-deficient mice after overloading. Dll4^flox/flox (Dll4^+/+) and Cdh5^CreERT2/+;Dll4^f/f (Dll4^–/–) mice were overloaded (OL) after TMX was intraperitoneally injected four times. i,j, Muscle weight (i) and OL-induced weight gain of PLA muscle (j) (n = 5). Muscle weights were normalised to body weight. Data represent the means ± s.e.m. and points represent individual mice. *P < 0.05, **P < 0.01, ***P < 0.001 as determined by: two-way ANOVA followed by Tukey’s multiple comparisons post-hoc test (c,f,i); Student’s two-tailed unpaired t-test (a,d,g,j).