PUBLICATION

Functional screening of congenital heart disease risk loci identifies 5 genes essential for heart development in zebrafish

Authors
Ma, J., Gu, Y., Liu, J., Song, J., Zhou, T., Jiang, M., Wen, Y., Guo, X., Zhou, Z., Sha, J., He, J., Hu, Z., Luo, L., Liu, M.
ID
ZDB-PUB-221228-3
Date
2022
Source
Cellular and molecular life sciences : CMLS   80: 1919 (Journal)
Registered Authors
He, Jianbo, Luo, Lingfei
Keywords
Cardiac development, Congenital heart malformation, Danio rerio, GWAS, Notch signaling
MeSH Terms
  • Animals
  • Genome-Wide Association Study
  • Heart
  • Heart Defects, Congenital*/genetics
  • Heart Septal Defects*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
PubMed
36574072 Full text @ Cell. Mol. Life Sci.
Abstract
Congenital heart disease (CHD) is the most common birth defect worldwide and a main cause of perinatal and infant mortality. Our previous genome-wide association study identified 53 SNPs that associated with CHD in the Han Chinese population. Here, we performed functional screening of 27 orthologous genes in zebrafish using injection of antisense morpholino oligos. From this screen, 5 genes were identified as essential for heart development, including iqgap2, ptprt, ptpn22, tbck and maml3. Presumptive roles of the novel CHD-related genes include heart chamber formation (iqgap2 and ptprt) and atrioventricular canal formation (ptpn22 and tbck). While deficiency of maml3 led to defective cardiac trabeculation and consequent heart failure in zebrafish embryos. Furthermore, we found that maml3 mutants showed decreased cardiomyocyte proliferation which caused a reduction in cardiac trabeculae due to inhibition of Notch signaling. Together, our study identifies 5 novel CHD-related genes that are essential for heart development in zebrafish and first demonstrates that maml3 is required for Notch signaling in vivo.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping