Qiang Lu
Yuanyuan Peng
Fang Geng
Xuelian Shao
Huili Zhou
Ying Cao
Ruilin Zhang
1 School of Life Sciences, Fudan University, Shanghai 200433, China;
2 Shanghai Medical College, Fudan University, Shanghai, China;
3 Department of Molecular and Cell Biology, School of Life Sciences and Technology, Tongji University, Shanghai 200331, China;
4 School of Basic Medical Sciences, Wuhan University, Wuhan 430072, China;
5 State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, China
Funds: This study was supported by National Key R&D Program of China grant 2018YFA0801004 and NSFC grant 31571492 to R.Z.
Received Date: 2019-12-20
Rev Recd Date:2020-02-07
Abstract
Abstract
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.Keywords: heart regeneration,
hemodynamics,
klf2,
Notch signaling,
primary cilia
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