ENS remodeling in mice with neuron-specific depletion of Hif1a or Vhl. (A) Confocal images of colonic myenteric plexus from tamoxifen- and 1×DSS- or water-treated SLICK-H^ER-CreHif1a^fl/fl (Cre⁺) and Hif1a^fl/fl (Cre^–) littermates, stained with MHCII (MMs), Hu (neuronal somas), and βIII-tubulin (nerve fibers) antibodies. Images are representative of control and DSS mice (DSS Cre^– and Cre⁺, n = 7 per group; baseline water Cre^–, n = 6). Scale bars, 100 μm. (B) Quantification of contacts between MMs and myenteric neurons in mice described in A by confocal microscopy (DSS Cre^– and Cre⁺, n = 7 per group). Baseline shows the mean value for tamoxifen- and water-treated Hif1a^fl/fl littermates (water Cre^–, n = 6). Data are shown as a distribution of pooled values generated from analysis of 5–8 fields of view per mouse per group. P values above each violet plot show statistical differences against baseline. (C) Structural changes in myenteric plexus of mice described in A quantified by confocal microscopy, showing counts of total neuron clusters, counts of Hu⁺ neurons per cluster, and counts and area of IGFT regions (DSS Cre^– and Cre⁺, n = 7 per group; baseline water Cre^–, n = 6). Data are shown as a distribution of pooled values generated from analysis of 5–8 fields of view per mouse per group. (D) Data same as in C shown as mean value per mouse per group (DSS Cre^– and Cre⁺, n = 7 per group; baseline water Cre^–, n = 6). P values above each column show statistical differences against baseline. (E) Complementary to Fig. 6 N: confocal images of colonic myenteric plexus from tamoxifen- and 3×DSS- or water-treated SLICK-H^ER-CreVhl^fl/fl (Cre⁺) and Vhl^fl/fl (Cre^–) littermates, stained with MHCII (MMs), Hu (neuronal somas), and βIII-tubulin (nerve fibers) antibodies. Images are representative of control and DSS mice (DSS Cre^– and Cre⁺, n = 4–7 per group; baseline water Cre^–, n = 2–3). Scale bars, 100 μm. (F) Complementary to Fig. 6 N: structural changes in myenteric plexus of mice described in E quantified by confocal microscopy, showing counts of total neuron clusters, counts of Hu⁺ neurons per cluster, and counts and area of IGFT regions (DSS Cre^– and Cre⁺, n = 4–7 per group; baseline water Cre^–, n = 2–3). Data same as in Fig. 6 N, shown as mean per mouse per group. P values above each column show statistical differences against baseline. All graphs show the mean ± SEM, n—mouse. Data are representative of at least two independent experiments with similar results. Statistical analyses: unpaired Student’s t test (B), one-way ANOVA (C and D), and two-way ANOVA for multiple comparisons (F), *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, and ****P ≤ 0.0001. # above pooled data in violin plots (B and C) indicates empirical P values calculated by the Nested Leave-One-Out Jackknife strategy, where ###P < 0.001.