1. BMP and Notch Signaling Pathways differentially regulate Cardiomyocyte Proliferation during Ventricle Regeneration
- Author
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Ye-Fan Hu, Nannan Chang, Chunxiao Yu, Qi Li, Ruilin Zhang, Meijun Pang, Wenyuan Wang, Yuanyuan Peng, and Jing-Wei Xiong
- Subjects
Cell cycle checkpoint ,heart regeneration ,BMP signaling ,Notch signaling pathway ,Applied Microbiology and Biotechnology ,Ubiquitin ,medicine ,Animals ,Regeneration ,Myocytes, Cardiac ,Molecular Biology ,Zebrafish ,Ecology, Evolution, Behavior and Systematics ,Notch signaling ,Cell Proliferation ,biology ,Receptors, Notch ,Regeneration (biology) ,cell-cycle arrest ,Ubiquitination ,Heart ,Cell Biology ,Bone Morphogenetic Protein Receptors ,Cell Cycle Checkpoints ,Cell cycle ,biology.organism_classification ,Cell biology ,medicine.anatomical_structure ,Ventricle ,cardiomyocyte proliferation ,biology.protein ,Signal transduction ,Developmental Biology ,Research Paper ,Signal Transduction - 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.
- Published
- 2021