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Real-Time ATP Imaging Reveals the Metabolic State during Branching Nephrogenesis.
Akiko Mii1, Shinya Yamamoto1, Masamichi Yamamoto1
1Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kidney360
|January 26, 2026
Summary
Ureteric bud branching during kidney development relies on glycolysis, with ureteric bud cells being more sensitive to its inhibition than mesenchyme cells. This highlights the critical role of metabolic regulation in nephrogenesis.
Area of Science:
- Developmental Biology
- Metabolic Regulation
- Renal Physiology
Background:
- Nephron formation is crucial for kidney development, but the underlying metabolic mechanisms are poorly understood.
- Intrauterine environment disturbances impact nephron endowment, increasing risks for hypertension and chronic kidney disease.
- Mechanisms linking metabolic status and nephron number during development require further investigation.
Purpose of the Study:
- To investigate the role of energy metabolism, specifically cytosolic adenosine 5-triphosphate (ATP) levels, in embryonic kidney development.
- To explore the spatiotemporal dynamics of ATP during nephrogenesis using advanced imaging techniques.
Main Methods:
- Utilized transgenic mice (GO-ATeam2) expressing a cytosolic ATP-FRET biosensor for live imaging of embryonic kidneys.
- Performed real-time ex vivo imaging of metanephric kidneys at single-cell resolution.
- Assessed the impact of glycolytic inhibition on ureteric bud branching and cell adhesion.
Main Results:
- Ureteric bud (UB) tip cells exhibited significantly lower ATP levels compared to UB stalk and cap mesenchyme (CM) cells during branching nephrogenesis.
- Glycolytic inhibition suppressed UB branching and reduced ATP levels in UB and CM cells, with a more pronounced effect on UB cells.
- Reduced glycolysis led to decreased UB branching, altered cell adhesion (N-cadherin expression), and disorganized CM cells, while oxidative phosphorylation inhibition had no such effects.
Conclusions:
- Branching nephrogenesis is highly dependent on glycolysis, particularly in UB cells during early development.
- UB cells are more sensitive to glycolytic inhibition than mesenchyme cells.
- Metabolic regulation, specifically glycolysis, plays a significant role in branching nephrogenesis.
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