PUBLICATION
Primary cilia mediate Klf2-dependant Notch activation in regenerating heart
- Authors
- Li, X., Lu, Q., Peng, Y., Geng, F., Shao, X., Zhou, H., Cao, Y., Zhang, R.
- ID
- ZDB-PUB-200422-33
- Date
- 2020
- Source
- Protein & cell 11(6): 433-445 (Journal)
- Registered Authors
- Cao, Ying, Zhang, Ruilin
- Keywords
- Notch signaling, heart regeneration, hemodynamics, klf2, primary cilia
- MeSH Terms
-
- Animals
- Cilia/metabolism*
- Kruppel-Like Transcription Factors/deficiency
- Kruppel-Like Transcription Factors/genetics
- Kruppel-Like Transcription Factors/metabolism*
- Myocardium/cytology
- Myocardium/metabolism*
- Myocytes, Cardiac/metabolism*
- Receptors, Notch/metabolism*
- Regeneration*
- Signal Transduction
- Zebrafish
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 32249387 Full text @ Protein Cell
Citation
Li, X., Lu, Q., Peng, Y., Geng, F., Shao, X., Zhou, H., Cao, Y., Zhang, R. (2020) Primary cilia mediate Klf2-dependant Notch activation in regenerating heart. Protein & cell. 11(6):433-445.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping