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Metabolic modulation regulates cardiac wall morphogenesis in zebrafish

Authors :
Ryuichi Fukuda
Alla Aharonov
Yu Ting Ong
Oliver A Stone
Mohamed El-Brolosy
Hans-Martin Maischein
Michael Potente
Eldad Tzahor
Didier YR Stainier
Source :
eLife, Vol 8 (2019)
Publication Year :
2019
Publisher :
eLife Sciences Publications Ltd, 2019.

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.

Details

Language :
English
ISSN :
2050084X
Volume :
8
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.b39dd6c217ae4752949b566bf0a577b0
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.50161