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Multi-scale simulation of early kidney branching morphogenesis
Wenran Cai1, Yunqi Wang2,3, Jicong Zhang2,3
1CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of China, Hefei, People's Republic of China.
Physical Biology
|January 4, 2021
Summary
Kidney branch tips avoid intersecting existing ducts through a repulsive mechanism, successfully reproduced by discrete simulations. This suggests glial cell line-derived neurotrophic factor concentration decay is key to early kidney development geometry.
Area of Science:
- Developmental Biology
- Computational Biology
- Biophysics
Background:
- Kidney development involves complex branch morphogenesis, characterized by tip termination on the kidney's outer surface.
- Preventing tip intersection with internal ducts is crucial for proper kidney structure formation.
Purpose of the Study:
- To model and simulate the mechanisms underlying branch morphogenesis in kidney development.
- To investigate the role of repulsive interactions in preventing branch intersection.
- To validate simulation findings against experimental observations of kidney branching patterns.
Main Methods:
- Transitioned from a continuous model to fast, discrete simulations incorporating coarse-grained rules.
- Implemented a ligand-receptor-based Turing mechanism to simulate branch-to-branch repulsion.
- Performed numerical simulations and analyzed geometrical parameters compared to experimental data from E15.5 kidneys.
Main Results:
- Successfully reproduced key features of experimentally observed kidney branch morphology using discrete simulations.
- Demonstrated that an exponentially decreasing repulsive effect between branches prevents their intersection.
- Found good agreement between simulated and experimental geometrical parameters.
Conclusions:
- The ligand-receptor-based Turing mechanism with distance-dependent repulsion is a viable model for kidney branch morphogenesis.
- Simulation results strongly support the hypothesis that glial cell line-derived neurotrophic factor concentration decay influences early kidney geometry.
