Histone deacetylase is required for the activation of Wnt/β-catenin signaling crucial for heart valve formation in zebrafish embryos

Kim, Y.S., Kim, M.J., Koo, T.H., Kim, J.D., Koun, S., Ham, H.J., Lee, Y.M., Rhee, M., Yeo, S.Y., and Huh, T.L.
Biochemical and Biophysical Research Communications   423(1): 140-146 (Journal)
Registered Authors
Huh, Tae-Lin, Kim, Jun-Dae, Kim, Myoung-Jin, Kim, Young-Seop, Koo, Tae-Hee, Koun, Soonil, Yeo, Sang-Yeob
zebrafish, heart valve, histone deacetylase, Bmp4, Wnt
MeSH Terms
  • Acetylation
  • Animals
  • Bone Morphogenetic Protein 4/biosynthesis
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Endocardial Cushions/embryology
  • Endocardium/embryology
  • Endocardium/metabolism
  • Gene Expression/drug effects
  • Heart Valves/abnormalities
  • Heart Valves/embryology*
  • Histone Deacetylase Inhibitors/pharmacology
  • Histone Deacetylases/genetics
  • Histone Deacetylases/metabolism*
  • Histones/metabolism
  • Hydroxamic Acids/pharmacology
  • Lithium Chloride/pharmacology
  • Myocardium/metabolism
  • Organogenesis/drug effects
  • Organogenesis/genetics
  • Receptor, Notch1/biosynthesis
  • Wnt Signaling Pathway*
  • Zebrafish/embryology*
  • Zebrafish/metabolism
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • beta Catenin/metabolism*
22634317 Full text @ Biochem. Biophys. Res. Commun.

During vertebrate heart valve formation, Wnt/β-catenin signaling induces BMP signals in atrioventricular canal (AVC) myocardial cells and underlying AVC endocardial cells then undergo endothelial-mesenchymal transdifferentiation (EMT) by receiving this BMP signals. Histone deacetylases (HDACs) have been implicated in numerous developmental processes by regulating gene expression. However, their specific roles in controlling heart valve development are largely unexplored. To investigate the role of HDACs in vertebrate heart valve formation, we treated zebrafish embryos with trichostatin A (TSA), an inhibitor of class I and II HDACs, from 36 to 48 h post-fertilization (hpf) during which heart looping and valve formation occur. Following TSA treatment, abnormal linear heart tube development was observed. In these embryos, expression of AVC myocardial bmp4 and AVC endocardial notch1b genes was markedly reduced with subsequent failure of EMT in the AVC endocardial cells. However, LiCl-mediated activation of Wnt/β-catenin signaling was able to rescue defective heart tube formation, bmp4 and notch1b expression, and EMT in the AVC region. Taken together, our results demonstrated that HDAC activity plays a pivotal role in vertebrate heart tube formation by activating Wnt/β-catenin signaling which induces bmp4 expression in AVC myocardial cells.

Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes