Image-based modeling of kidney branching morphogenesis reveals GDNF-RET based Turing-type mechanism and
Denis Menshykau1,2, Odyssé Michos3,4,5, Christine Lang3,4
1Department for Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058, Basel, Switzerland. denis.menshykau@gmail.com.
Nature Communications
|January 18, 2019
Summary
A common Turing mechanism guides organ branching. This ligand-receptor model, using GDNF for kidneys and FGF10/SHH for lungs, explains diverse branching patterns and tip packing.
Area of Science:
- Developmental Biology
- Systems Biology
- Organogenesis
Background:
- Organ branching patterns and regulatory networks vary significantly across different organs.
- The existence of a common regulatory mechanism for branching morphogenesis remains an open question.
- Previous models, like the FGF10/SHH Turing mechanism, have successfully explained lung branching.
Purpose of the Study:
- To investigate if a common ligand-receptor-based Turing mechanism underlies branching in different organs, specifically the kidney.
- To determine how organ-specific branching patterns emerge from a general mechanism.
- To explore the role of GDNF and WNT11 in kidney ureteric bud branching.
Main Methods:
- Utilized a Glial cell line-Derived Neurotrophic Factor (GDNF)-dependent ligand-receptor-based Turing mechanism to model ureteric bud branching.
- Cultured wildtype and mutant ureteric buds to validate the model.
- Employed in silico simulations to direct domain outgrowth and predict branching patterns.
- Experimentally confirmed the positive feedback loop between WNT11 and GDNF in kidney tip packing.
Main Results:
- The GDNF-dependent Turing mechanism quantitatively recapitulated branching patterns in cultured ureteric buds.
- In silico simulations demonstrated the mechanism's ability to achieve similar branching patterns.
- A kidney-specific positive feedback between WNT11 and GDNF was identified, enabling dense packing of ureteric tips.
- The model successfully predicted and explained observed branching phenomena.
Conclusions:
- The ligand-receptor-based Turing mechanism provides a common regulatory framework for branching morphogenesis in both lungs and kidneys.
- Molecular differences in ligand-receptor implementation allow for organ-specific branching patterns.
- The identified mechanism is flexible and robust, suggesting its potential as a general principle for guiding organogenesis and other symmetry-breaking events.
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