PUBLICATION
Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart
- Authors
- Lowe, V., Wisniewski, L., Sayers, J., Evans, I., Frankel, P., Mercader-Huber, N., Zachary, I.C., Pellet-Many, C.
- ID
- ZDB-PUB-190608-1
- Date
- 2019
- Source
- Development (Cambridge, England) 146(13): (Journal)
- Registered Authors
- Keywords
- Epicardium, Heart, Neuropilin, Regeneration, Zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Movement/genetics
- Cells, Cultured
- Cold Temperature
- Coronary Vessels/physiology
- Heart/physiology*
- Heart Injuries/etiology
- Heart Injuries/pathology
- Heart Injuries/physiopathology
- Myocytes, Cardiac/physiology
- Neovascularization, Physiologic/genetics*
- Neuropilin-1/genetics
- Neuropilin-1/physiology*
- Pericardium/physiology*
- Rats
- Regeneration/genetics*
- Zebrafish/physiology
- PubMed
- 31167777 Full text @ Development
Citation
Lowe, V., Wisniewski, L., Sayers, J., Evans, I., Frankel, P., Mercader-Huber, N., Zachary, I.C., Pellet-Many, C. (2019) Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart. Development (Cambridge, England). 146(13):.
Abstract
Unlike adult mammals, zebrafish can regenerate their heart. A key mechanism for regeneration is the activation of the epicardium, leading to the establishment of a supporting scaffold for new cardiomyocytes, angiogenesis and cytokine secretion. Neuropilins are co-receptors mediating signaling of kinase receptors for cytokines known to play critical roles in zebrafish heart regeneration. We investigated the role of neuropilins in response to cardiac injury and heart regeneration. All four neuropilin isoforms nrp1a, nrp1b, nrp2a and nrp2b were upregulated by the activated epicardium and a nrp1a knockout mutant showed a significant delay in heart regeneration and displayed persistent collagen deposition. The regenerating hearts of nrp1a mutants were less vascularized and epicardial-derived cell migration and re-expression of the developmental gene wt1b was impaired. Moreover, cryoinjury-induced activation and migration of epicardial cells in heart explants was reduced in nrp1a mutant. These results identify a key role for Nrp1 in zebrafish heart regeneration, mediated through epicardial activation, migration and revascularization.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping