PUBLICATION

BMP and Notch Signaling Pathways differentially regulate Cardiomyocyte Proliferation during Ventricle Regeneration

Authors
Wang, W., Hu, Y.F., Pang, M., Chang, N., Yu, C., Li, Q., Xiong, J.W., Peng, Y., Zhang, R.
ID
ZDB-PUB-210710-3
Date
2021
Source
International journal of biological sciences   17: 2157-2166 (Journal)
Registered Authors
Zhang, Ruilin
Keywords
BMP signaling, Notch signaling, cardiomyocyte proliferation, cell-cycle arrest, heart regeneration
MeSH Terms
  • Animals
  • Bone Morphogenetic Protein Receptors/metabolism*
  • Cell Cycle Checkpoints
  • Cell Proliferation
  • Heart/physiology*
  • Myocytes, Cardiac/cytology*
  • Myocytes, Cardiac/metabolism
  • Receptors, Notch/metabolism*
  • Regeneration*
  • Signal Transduction*
  • Ubiquitination
  • Zebrafish/physiology
PubMed
34239346 Full text @ Int. J. Biol. Sci.
Abstract
Adult mammalian hearts show limited capacity to proliferate after injury, while zebrafish are capable to completely regenerate injured hearts through the proliferation of spared cardiomyocytes. BMP and Notch signaling pathways have been implicated in cardiomyocyte proliferation during zebrafish heart regeneration. However, the molecular mechanism underneath this process as well as the interaction between these two pathways remains to be further explored. In this study we showed BMP signaling was activated after ventricle ablation and acted epistatic downstream of Notch signaling. Inhibition of both signaling pathways differentially influenced ventricle regeneration and cardiomyocyte proliferation, as revealed by time-lapse analysis using a cardiomyocyte-specific FUCCI (fluorescent ubiquitylation-based cell cycle indicator) system. Further experiments revealed that inhibition of BMP and Notch signaling led to cell-cycle arrest at different phases. Overall, our results shed light on the interaction between BMP and Notch signaling pathways and their functions in cardiomyocyte proliferation during cardiac regeneration.
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