Zebrafish foxc1a controls ventricular chamber maturation by directly regulating wwtr1 and nkx2.5 expression
- He, L., Zhang, Q., Jiang, D., Zhang, Y., Wei, Y., Yang, Y., Li, N., Wang, S., Yue, Y., Zhao, Q.
- Journal of genetics and genomics = Yi chuan xue bao 49(6): 559-568 (Journal)
- Registered Authors
- Yue, Yunyun, Zhao, Qingshun
- cardiac ventricular development, foxc1a, nkx2.5, wwtr1, zebrafish
- MeSH Terms
- Gene Expression Regulation, Developmental
- Myocytes, Cardiac/metabolism
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- 34923164 Full text @ J. Genet. Genomics
He, L., Zhang, Q., Jiang, D., Zhang, Y., Wei, Y., Yang, Y., Li, N., Wang, S., Yue, Y., Zhao, Q. (2021) Zebrafish foxc1a controls ventricular chamber maturation by directly regulating wwtr1 and nkx2.5 expression. Journal of genetics and genomics = Yi chuan xue bao. 49(6):559-568.
Chamber maturation is a significant process in cardiac development. Disorders of this crucial process lead to a range of congenital heart defects. Foxc1a is a critical transcription factor reported to regulate the specification of cardiac progenitor cells. However, little is known about the role of Foxc1a in modulating chamber maturation. Previously, we reported that foxc1a-null zebrafish embryos exhibit disrupted heart structures and functions. In this study, we observed that ventricle structure and cardiomyocyte proliferation were abolished during chamber maturation in foxc1a-null zebrafish embryos. To observe the endogenous localization of Foxc1a in the hearts of living embryos, we inserted eyfp at the foxc1a genomic locus using TALEN. Analysis of the knockin zebrafish showed that foxc1a was widely expressed in ventricular cardiomyocytes during chamber development. Cardiac RNA sequencing analysis revealed downregulated expression of the Hippo signaling effector wwtr1. Dual-luciferase and chromatin immunoprecipitation assays revealed that Foxc1a could bind directly to three sites in the wwtr1 promoter region. Furthermore, wwtr1 mRNA overexpression was sufficient to reverse the ventricle defects during chamber maturation. Conditional overexpression of nkx2.5 also partially rescued the ventricular defects during chamber development. These findings demonstrate that wwtr1 and nkx2.5 are direct targets of Foxc1a during ventricular chamber maturation.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes