TY - JOUR
T1 - Metabolic modulation regulates cardiac wall morphogenesis in zebrafish
AU - Fukuda, Ryuichi
AU - Aharonov, Alla
AU - Ong, Yu Ting
AU - Stone, Oliver A.
AU - El-Brolosy, Mohamed
AU - Maischein, Hans-Martin
AU - Potente, Michael
AU - Tzahor, Eldad
AU - Stainier, Didier Y. R.
N1 - Funding: Max-Planck-Gesellschaft (Open-access funding) Didier YR Stainier The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Acknowledgements We thank Beate Grohmann, Radhan Ramadass, Srinath Ramkumar, Simon Perathoner, Carmen Büttner, Nana Fukuda and Sharon Meaney-Gardian for help and support, Arica Beisaw, Ruben Marin-Juez, Josephine Gollin and Rashmi Priya for comments on the manuscript, and Jeroen Bakkers for communication. This work was supported in part by funds from the Max Planck Society to DYRS.
PY - 2019/12/23
Y1 - 2019/12/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85077691291&partnerID=8YFLogxK
U2 - https://doi.org/10.7554/eLife.50161
DO - https://doi.org/10.7554/eLife.50161
M3 - مقالة
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - 50161
ER -