PUBLICATION
Reactivation of Notch signaling is required for cardiac valve regeneration
- Authors
- Kefalos, P., Agalou, A., Kawakami, K., Beis, D.
- ID
- ZDB-PUB-191108-16
- Date
- 2019
- Source
- Scientific Reports 9: 16059 (Journal)
- Registered Authors
- Beis, Dimitris, Kawakami, Koichi
- Keywords
- none
- MeSH Terms
-
- Animals
- Embryo, Nonmammalian/embryology*
- Embryonic Development*
- Gene Expression Regulation, Developmental*
- Heart Valve Diseases/embryology*
- Heart Valves/physiology*
- Receptor, Notch1/biosynthesis*
- Regeneration*
- Signal Transduction*
- Zebrafish/embryology*
- Zebrafish Proteins/biosynthesis*
- PubMed
- 31690782 Full text @ Sci. Rep.
Citation
Kefalos, P., Agalou, A., Kawakami, K., Beis, D. (2019) Reactivation of Notch signaling is required for cardiac valve regeneration. Scientific Reports. 9:16059.
Abstract
Cardiac Valve Disease is one of the most common heart disorders with an emerging epidemic of cardiac valve degeneration due to aging. Zebrafish can regenerate most of their organs, including their heart. We aimed to explore the regenerative potential of cardiac valves and the underlying molecular mechanisms involved. We used an inducible, tissue-specific system of chemogenetic ablation and showed that zebrafish can also regenerate their cardiac valves. Upon valvular damage at larval stages, the intracardiac flow pattern becomes reminiscent of the early embryonic stages, exhibiting an increase in the retrograde flow fraction through the atrioventricular canal. As a result of the altered hemodynamics, notch1b and klf2a expression are ectopically upregulated, adopting the expression pattern of earlier developmental stages. We find that Notch signaling is re-activated upon valvular damage both at larval and adult stages and that it is required during the initial regeneration phase of cardiac valves. Our results introduce an animal model of cardiac valve specific ablation and regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping