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Metabolic modulation regulates cardiac wall morphogenesis in zebrafish

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Item Type:Article
Title:Metabolic modulation regulates cardiac wall morphogenesis in zebrafish
Creators Name:Fukuda, R. and Aharonov, A. and Ong, Y.T. and Stone, O.A. and El-Brolosy, M. and Maischein, H.M. and Potente, M. and Tzahor, El. and Stainier, D.Y.R.
Abstract: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.
Keywords:Animal Models, Cardiac Myocytes, Cell Proliferation, Developmental Gene Expression Regulation, erbB-2 Genes, Genetically Modified Animals, Glycolysis, Heart, Morphogenesis, Organogenesis, Signal Transduction, Zebrafish Proteins, Animals, Rats, Zebrafish
Publisher:eLife Sciences Publications
Date:23 December 2019
Official Publication:https://doi.org/10.7554/eLife.50161
PubMed:View item in PubMed

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