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Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart

Lowe, V; Wisniewski, L; Sayers, J; Evans, I; Frankel, P; Mercader-Huber, N; Zachary, I C; Pellet-Many, C

Authors

V Lowe

L Wisniewski

J Sayers

I Evans

P Frankel

N Mercader-Huber

I C Zachary

C Pellet-Many



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.

Citation

Lowe, V., Wisniewski, L., Sayers, J., Evans, I., Frankel, P., Mercader-Huber, N., …Pellet-Many, C. (2019). Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart. Development, 146, https://doi.org/10.1242/dev.174482

Journal Article Type Article
Acceptance Date May 14, 2019
Publication Date Jun 5, 2019
Deposit Date Jun 25, 2019
Publicly Available Date Jun 28, 2019
Journal DEVELOPMENT
Print ISSN 1011-6370
Publisher The Company of Biologists
Peer Reviewed Peer Reviewed
Volume 146
DOI https://doi.org/10.1242/dev.174482
Public URL https://rvc-repository.worktribe.com/output/1381978

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