Planar cell polarity genes frizzled4 and frizzled6 exert patterning influence on arterial vessel morphogenesis.

摘要: Quantitative analysis of the vascular network anatomy is critical for understanding vasculature structure and function. In this study, we have combined microcomputed tomography (microCT) computational to provide quantitative three-dimensional geometrical topological characterization normal kidney vasculature, investigate how 2 core genes Wnt/planar cell polarity, Frizzled4 Frizzled6, affect morphogenesis. Experiments were performed on frizzled4 (Fzd4-/-) frizzled6 (Fzd6-/-) deleted mice littermate controls (WT) perfused with a contrast medium after euthanasia exsanguination. The kidneys scanned high-resolution (16 μm) microCT imaging system, followed by 3D reconstruction arterial vasculature. Computational treatment includes decomposition networks based Diameter-Defined Strahler Order (DDSO). We calculated (i) Global scale parameters, such as volume its fractal dimension (ii) Structural parameters depending DDSO hierarchical levels ordering, diameter, length branching angles vessel segments, (iii) Functional estimated resistance blood flow alongside tree average density terminal arterioles. kidneys, was 2.07±0.11 (n = 7), significantly lower in Fzd4-/- (1.71±0.04; n 4), Fzd6-/- (1.54±0.09; 3) kidneys. number 5 WT Fzd4-/-, only 4 Fzd6-/-. Scaling characteristics diameter segments altered mutants, whereas bifurcation not different from WT. Fzd4 Fzd6 deletion increased resistance, using Hagen-Poiseuille equation, each DDSO, decreased homogeneity distal segments. Our results show that our methodology suitable networks, deep patterning effect morphogenesis may determine functional efficiency.