PUBLICATION

A novel gene-trap line reveals the dynamic patterns and essential roles of cysteine and glycine-rich protein 3 in zebrafish heart development and regeneration

Authors
Liang, S., Zhou, Y., Chang, Y., Li, J., Zhang, M., Gao, P., Li, Q., Yu, H., Kawakami, K., Ma, J., Zhang, R.
ID
ZDB-PUB-240401-6
Date
2024
Source
Cellular and molecular life sciences : CMLS   81: 158158 (Journal)
Registered Authors
Kawakami, Koichi, Zhang, Ruilin
Keywords
csrp3/mlp, Gene-trap, Heart development, Heart regeneration, Trabeculation
MeSH Terms
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Muscle Proteins/genetics
  • Muscle Proteins/metabolism
  • Animals
  • Myocytes, Cardiac/metabolism
  • Cysteine/genetics
  • Cysteine/metabolism
  • Humans
  • Cardiomyopathy, Hypertrophic*/genetics
  • Cardiomyopathy, Hypertrophic*/metabolism
  • LIM Domain Proteins*
(all 12)
PubMed
38556571 Full text @ Cell. Mol. Life Sci.
Abstract
Mutations in cysteine and glycine-rich protein 3 (CSRP3)/muscle LIM protein (MLP), a key regulator of striated muscle function, have been linked to hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in patients. However, the roles of CSRP3 in heart development and regeneration are not completely understood. In this study, we characterized a novel zebrafish gene-trap line, gSAIzGFFM218A, which harbors an insertion in the csrp3 genomic locus, heterozygous fish served as a csrp3 expression reporter line and homozygous fish served as a csrp3 mutant line. We discovered that csrp3 is specifically expressed in larval ventricular cardiomyocytes (CMs) and that csrp3 deficiency leads to excessive trabeculation, a common feature of CSRP3-related HCM and DCM. We further revealed that csrp3 expression increased in response to different cardiac injuries and was regulated by several signaling pathways vital for heart regeneration. Csrp3 deficiency impeded zebrafish heart regeneration by impairing CM dedifferentiation, hindering sarcomere reassembly, and reducing CM proliferation while aggravating apoptosis. Csrp3 overexpression promoted CM proliferation after injury and ameliorated the impairment of ventricle regeneration caused by pharmacological inhibition of multiple signaling pathways. Our study highlights the critical role of Csrp3 in both zebrafish heart development and regeneration, and provides a valuable animal model for further functional exploration that will shed light on the molecular pathogenesis of CSRP3-related human cardiac diseases.
Errata / Notes
Corrected by: ZDB-PUB-240911-6
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f2TgTransgenic Insertion
    mw43TgTransgenic Insertion
      nkgsaizgffm218aTgTransgenic Insertion
      s957TgTransgenic Insertion
        whu314TgTransgenic Insertion
          zf2119TgTransgenic Insertion
            zf3347TgTransgenic Insertion
              1 - 7 of 7
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              Target Reagent Reagent Type
              tnnt2aMO1-tnnt2aMRPHLNO
              1 - 1 of 1
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              Fish
              No data available
              Antibodies
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              DsRed2EFGDsRed2
              EGFPEFGEGFP
              GAL4FFEFGGAL4FF
              GFPEFGGFP
              mCherryEFGmCherry
              1 - 5 of 5
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              Mapping
              No data available
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              Citation
              Liang, S., Zhou, Y., Chang, Y., Li, J., Zhang, M., Gao, P., Li, Q., Yu, H., Kawakami, K., Ma, J., Zhang, R. (2024) A novel gene-trap line reveals the dynamic patterns and essential roles of cysteine and glycine-rich protein 3 in zebrafish heart development and regeneration. Cellular and molecular life sciences : CMLS. 81:158158.