PUBLICATION
Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming
- Authors
- Gálvez-Santisteban, M., Chen, D., Zhang, R., Serrano, R., Nguyen, C., Zhao, L., Nerb, L., Masutani, E.M., Vermot, J., Burns, C.G., Burns, C.E., Del Álamo, J.C., Chi, N.C.
- ID
- ZDB-PUB-190627-8
- Date
- 2019
- Source
- eLIFE 8: (Journal)
- Registered Authors
- Burns (Erter), Caroline, Chi, Neil C., Vermot, Julien, Zhang, Ruilin, Zhao, Long
- Keywords
- developmental biology, genetics, heart, hemodynamics, regeneration, reprogramming, zebrafish
- MeSH Terms
-
- Animals
- Endocardium/physiology*
- Heart Injuries/pathology*
- Hemodynamics*
- Kruppel-Like Transcription Factors/metabolism
- Mechanotransduction, Cellular*
- Myocytes, Cardiac/physiology*
- Receptors, Notch/metabolism
- Regeneration*
- TRPV Cation Channels/metabolism
- Zebrafish
- Zebrafish Proteins/metabolism
- PubMed
- 31237233 Full text @ Elife
Citation
Gálvez-Santisteban, M., Chen, D., Zhang, R., Serrano, R., Nguyen, C., Zhao, L., Nerb, L., Masutani, E.M., Vermot, J., Burns, C.G., Burns, C.E., Del Álamo, J.C., Chi, N.C. (2019) Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming. eLIFE. 8:.
Abstract
Lower vertebrate and neonatal mammalian hearts exhibit the remarkable capacity to regenerate through the reprogramming of pre-existing cardiomyocytes. However, how cardiac injury initiates signaling pathways controlling this regenerative reprogramming remains to be defined. Here, we utilize in vivo biophysical and genetic fate mapping zebrafish studies to reveal that altered hemodynamic forces due to cardiac injury activate a sequential endocardial-myocardial signaling cascade to direct cardiomyocyte reprogramming and heart regeneration. Specifically, these altered forces are sensed by the endocardium through the mechanosensitive channel Trpv4 to control Klf2a transcription factor expression. Consequently, Klf2a then activates endocardial Notch signaling which results in the non-cell autonomous initiation of myocardial Erbb2 and BMP signaling to promote cardiomyocyte reprogramming and heart regeneration. Overall, these findings not only reveal how the heart senses and adaptively responds to environmental changes due to cardiac injury, but also provide insight into how flow-mediated mechanisms may regulate cardiomyocyte reprogramming and heart regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping