Metabolic modulation regulates cardiac wall morphogenesis in zebrafish
| Autor: | Alla Aharonov, Oliver A. Stone, Didier Y.R. Stainier, Yu Ting Ong, Ryuichi Fukuda, Michael Potente, Eldad Tzahor, Hans-Martin Maischein, Mohamed A. El-Brolosy |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
QH301-705.5 Science Cell Morphogenesis cardiomyocytes General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine medicine Glycolysis trabeculation Biology (General) Zebrafish General Immunology and Microbiology biology Heart development Chemistry General Neuroscience Cell Biology General Medicine Metabolism heart development glycolysis biology.organism_classification zebrafish Cell biology 030104 developmental biology medicine.anatomical_structure Cardiovascular and Metabolic Diseases 030220 oncology & carcinogenesis Medicine Developmental biology metabolism Pyruvate kinase Research Article Developmental Biology |
| Zdroj: | eLife, Vol 8 (2019) eLife |
| Popis: | During cardiac development, cardiomyocytes form complex inner wall structures called trabeculae. Despite significant investigation into this process, the potential role of metabolism has not been addressed. Using single cell resolution imaging in zebrafish, we find that cardiomyocytes seeding the trabecular layer actively change their shape while compact layer cardiomyocytes remain static. We show that Erbb2 signaling, which is required for trabeculation, activates glycolysis to support changes in cardiomyocyte shape and behavior. Pharmacological inhibition of glycolysis impairs cardiac trabeculation, and cardiomyocyte-specific loss- and gain-of-function manipulations of glycolysis decrease and increase trabeculation, respectively. In addition, loss of the glycolytic enzyme pyruvate kinase M2 impairs trabeculation. Experiments with rat neonatal cardiomyocytes in culture further support these observations. Our findings reveal new roles for glycolysis in regulating cardiomyocyte behavior during cardiac wall morphogenesis. |
| Databáze: | OpenAIRE |
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