Planar cell polarity genes frizzled4 and frizzled6 exert patterning influence on arterial vessel morphogenesisReport as inadecuate

Planar cell polarity genes frizzled4 and frizzled6 exert patterning influence on arterial vessel morphogenesis - Download this document for free, or read online. Document in PDF available to download.

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

Author: Rene Markovič , Julien Peltan , Marko Gosak, Denis Horvat, Borut Žalik, Benjamin Seguy, Remi Chauvel, Gregoire Malandain, Thier



Related documents