Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart.
Vanessa LoweLaura WisniewskiJacob SayersIan EvansPaul FrankelNadia MercaderIan C ZacharyCaroline Pellet-ManyPublished in: Development (Cambridge, England) (2019)
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 that mediate signaling of kinase receptors for cytokines with crucial 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 an 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 were reduced in nrp1a mutants. These results identify a key role for Nrp1 in zebrafish heart regeneration, mediated through epicardial activation, migration and revascularization.
Keyphrases
- stem cells
- heart failure
- atrial fibrillation
- wound healing
- cell migration
- poor prognosis
- coronary artery bypass grafting
- gene expression
- coronary artery disease
- percutaneous coronary intervention
- endothelial cells
- left ventricular
- high glucose
- acute coronary syndrome
- signaling pathway
- genome wide
- wild type
- high resolution
- drug induced
- cell cycle arrest
- genome wide analysis