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Metabolic modulation regulates cardiac wall morphogenesis in zebrafish
Ryuichi Fukuda1, Alla Aharonov2, Yu Ting Ong3
1Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Ludwigstrasse, Germany.
Elife
|December 24, 2019
Summary
Glycolysis fuels cardiomyocyte shape changes essential for forming heart trabeculae during development. This metabolic pathway is critical for cardiac wall morphogenesis and trabeculation.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Cellular Metabolism
Background:
- Cardiomyocytes form intricate trabeculae during heart development.
- The metabolic regulation of this process remains largely unexplored.
Purpose of the Study:
- To investigate the role of metabolism, specifically glycolysis, in cardiomyocyte behavior during cardiac trabeculation.
- To elucidate the molecular mechanisms linking Erbb2 signaling, glycolysis, and trabeculation.
Main Methods:
- Single-cell resolution imaging in zebrafish embryos.
- Pharmacological inhibition of glycolysis.
- Cardiomyocyte-specific genetic manipulation of glycolysis (loss- and gain-of-function).
- Biochemical assays involving pyruvate kinase M2.
- Experiments with rat neonatal cardiomyocytes in culture.
Main Results:
- Trabecular cardiomyocytes exhibit dynamic shape changes, unlike static compact layer cardiomyocytes.
- Erbb2 signaling activates glycolysis, supporting cardiomyocyte shape and behavior.
- Glycolysis inhibition or manipulation impairs cardiac trabeculation.
- Loss of pyruvate kinase M2 disrupts trabeculation.
Conclusions:
- Glycolysis plays a crucial role in regulating cardiomyocyte behavior during cardiac wall morphogenesis.
- Metabolic reprogramming, particularly enhanced glycolysis, is essential for successful cardiac trabeculation.
