PUBLICATION
Cardiac Na+-Ca2+ exchanger 1 (ncx1h) is critical for the ventricular cardiomyocyte formation via regulating the expression levels of gata4 and hand2 in zebrafish
- Authors
- Chu, L., Yin, H., Gao, L., Gao, L., Xia, Y., Zhang, C., Chen, Y., Liu, T., Huang, J., Boheler, K.R., Zhou, Y., Yang, H.T.
- ID
- ZDB-PUB-200711-10
- Date
- 2020
- Source
- Science China. Life sciences 64(2): 255-268 (Journal)
- Registered Authors
- Chen, Yi
- Keywords
- Ca2+ transport protein, gata4, hand2, ncx1h, ventricular cardiomyocyte formation, zebrafish
- MeSH Terms
-
- Calcium/metabolism
- Heart Ventricles/cytology
- Heart Ventricles/embryology
- Heart Ventricles/metabolism
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Animals
- Gene Expression Regulation, Developmental*
- Animals, Genetically Modified
- GATA Transcription Factors/genetics*
- GATA Transcription Factors/metabolism
- Mutation
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish/metabolism
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/metabolism*
- Sodium-Calcium Exchanger/genetics*
- Sodium-Calcium Exchanger/metabolism
- Basic Helix-Loop-Helix Transcription Factors/genetics*
- Basic Helix-Loop-Helix Transcription Factors/metabolism
- In Situ Hybridization
- Microscopy, Confocal
- Organogenesis/genetics
- PubMed
- 32648190 Full text @ Sci. China Ser. C-Life Sci.
Citation
Chu, L., Yin, H., Gao, L., Gao, L., Xia, Y., Zhang, C., Chen, Y., Liu, T., Huang, J., Boheler, K.R., Zhou, Y., Yang, H.T. (2020) Cardiac Na+-Ca2+ exchanger 1 (ncx1h) is critical for the ventricular cardiomyocyte formation via regulating the expression levels of gata4 and hand2 in zebrafish. Science China. Life sciences. 64(2):255-268.
Abstract
Ca2+ signaling is critical for heart development; however, the precise roles and regulatory pathways of Ca2+ transport proteins in cardiogenesis remain largely unknown. Sodium-calcium exchanger 1 (Ncx1) is responsible for Ca2+ efflux in cardiomyocytes. It is involved in cardiogenesis, while the mechanism is unclear. Here, using the forward genetic screening in zebrafish, we identified a novel mutation at a highly-conserved leucine residue in ncx1 gene (mutantLDD353/ncx1hL154P) that led to smaller hearts with reduced heart rate and weak contraction. Mechanistically, the number of ventricular but not atrial cardiomyocytes was reduced in ncx1hL154P zebrafish. These defects were mimicked by knockdown or knockout of ncx1h. Moreover, ncx1hL154P had cytosolic and mitochondrial Ca2+ overloading and Ca2+ transient suppression in cardiomyocytes. Furthermore, ncx1hL154P and ncx1h morphants downregulated cardiac transcription factors hand2 and gata4 in the cardiac regions, while overexpression of hand2 and gata4 partially rescued cardiac defects including the number of ventricular myocytes. These findings demonstrate an essential role of the novel 154th leucine residue in the maintenance of Ncx1 function in zebrafish, and reveal previous unrecognized critical roles of the 154th leucine residue and Ncx1 in the formation of ventricular cardiomyocytes by at least partially regulating the expression levels of gata4 and hand2.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping