Unlike adult mammalian heart, zebrafish heart has a remarkable capacity to regenerate after injury. Previous study has shown Notch signaling activation in the endocardium is essential for regeneration of the myocardium and this activation is mediated by hemodynamic alteration after injury, however, the molecular mechanism has not been fully explored. In this study we demonstrated that blood flow change could be perceived and transmitted in a primary cilia dependent manner to control the hemodynamic responsive klf2 gene expression and subsequent activation of Notch signaling in the endocardium. First we showed that both homologues of human gene KLF2 in zebrafish, klf2a and klf2b, could respond to hemodynamic alteration and both were required for Notch signaling activation and heart regeneration. Further experiments indicated that the upregulation of klf2 gene expression was mediated by endocardial primary cilia. Overall, our findings reveal a novel aspect of mechanical shear stress signal in activating Notch pathway and regulating cardiac regeneration.

Atherosclerotic cardiovascular disease is one of the leading causes of death worldwide. Establishing animal models of atherosclerosis is of great benefit for studying its complicated pathogenesis and screening and evaluating related drugs. Although researchers have generated a variety of models for atherosclerosis study in rabbits, mice and rats, the limitations of these models make it difficult to monitor the development of atherosclerosis, and these models are unsuitable for large scale screening of potential therapeutic targets. On the contrast, zebrafish can fulfill these purposes thanks to their fecundity, rapid development ex utero, embryonic transparency, and conserved lipid metabolism process. Thus, zebrafish have become a popular alternative animal model for atherosclerosis research. In this mini review, we summarize different zebrafish models used to study atherosclerosis, focusing on the latest applications of these models to the dynamic monitoring of atherosclerosis progression, mechanistic study of therapeutic intervention and drug screening, and assessment of the impacts of other risk factors.

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.