Fig. 4: BMP signaling promotes anoikis by suppressing integrin expression.
From: Positional BMP signaling orchestrates villus length in the small intestine
a TUNEL assay (control and Bmpr1a cKO mice) with grayscale enlargements. TUNEL+ cells quantified across intestinal regions (Villus lengths-scaled) with error bars representing the standard deviation (SD), visualized as shaded regions in the plots. N = 3 mice/group. Scale bars, 200 µm. b Two-stage cell lineage model: progenitor cell proliferation and differentiation leading to cell death (d_1) controlled by BMP activity (Created in BioRender. Liu (2025) https://BioRender.com/jyzljkj). c Computational modeling shows that BMP signaling progressively amplifies during villus elongation (t1–t8). Distal segments, which exhibit lower expression and diffusion rate of Grem1, develop earlier and stronger BMP peaks compared to proximal regions. d Simulated villus growth (proximal/distal) with progenitor cell proportions. The dashed line marks the crypt-villus boundary. e Model prediction of BMP signaling activity in the apical cells of the villi upon reaching a state of equilibrium in villus growth. f p-Smad1/5 and TUNEL intensity profiles along villus (proximal P6 vs distal D3 positions). P6, 6th position from a base in the proximal segment. D3, 3rd position from base in the distal segment. g Integrin gene heatmap (control vs cKO). N = 3 mice/group. h Immunofluorescence staining and quantification of integrin α6 with error bars representing the standard deviation (SD), visualized as shaded regions in the plots. N = 3 mice/group. Scale bars, 200 µm. i Organoid immunoblots (48 h treatments: E [EGF], N [Noggin], R [R-spondin], B [BMP 6.7/20 ng/mL]). N = 3 cultures. N = 3 independent organoid cultures. j Ki67 staining and villus length quantification in control and Pyrintegrin-injected mice. N = 3 mice/group. Scale bars, 200 µm. The white arrows indicated the apex of the villus. k Villus growth prediction under the threshold mechanism, modifying the differentiated cell removal rate (d_1) using a Hill equation. l Villus length modeling under different conditions (WT, constant d_1, γ_B = 0) of the model shown in Fig. 4b. m EdU+ cells 24 h after injection. N = 3 mice/group. Scale bars, 200 µm. The data were analyzed by two-way ANOVA with Tukey’s multiple comparison test (i) and unpaired t-test with Welch-correction (two-sided) (m). Data represent mean ± SD.
