PUBLICATION
Metabolic modulation regulates cardiac wall morphogenesis in zebrafish
- Authors
- Fukuda, R., Aharonov, A., Ong, Y.T., Stone, O.A., El-Brolosy, M., Maischein, H.M., Potente, M., Tzahor, E., Stainier, D.Y.
- ID
- ZDB-PUB-191226-12
- Date
- 2019
- Source
- eLIFE 8: (Journal)
- Registered Authors
- Keywords
- cell biology, developmental biology, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Proliferation
- Gene Expression Regulation, Developmental
- Genes, erbB-2/genetics
- Glycolysis
- Heart/embryology*
- Heart/growth & development*
- Heart/physiology
- Models, Animal
- Morphogenesis/genetics
- Morphogenesis/physiology*
- Myocytes, Cardiac/metabolism*
- Organogenesis/genetics
- Organogenesis/physiology
- Rats
- Signal Transduction/physiology
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/growth & development*
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 31868165 Full text @ Elife
Citation
Fukuda, R., Aharonov, A., Ong, Y.T., Stone, O.A., El-Brolosy, M., Maischein, H.M., Potente, M., Tzahor, E., Stainier, D.Y. (2019) Metabolic modulation regulates cardiac wall morphogenesis in zebrafish. eLIFE. 8:.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping