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Development. 2019 Jul 2;146(13). pii: dev174482. doi: 10.1242/dev.174482.

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

Author information

1
Centre for Cardiovascular Biology and Medicine, Division of Medicine, The Rayne Building, University College London, London WC1E 6JJ, UK.
2
Department of Developmental Biology and Regeneration, Institut für Anatomie, Universität Bern, Baltzerstrasse 2, 3012 Bern, Switzerland.
3
Centre for Cardiovascular Biology and Medicine, Division of Medicine, The Rayne Building, University College London, London WC1E 6JJ, UK c.pellet-many@ucl.ac.uk i.zachary@ucl.ac.uk.
4
Department of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK c.pellet-many@ucl.ac.uk i.zachary@ucl.ac.uk.

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 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.

KEYWORDS:

Epicardium; Heart; Neuropilin; Regeneration; Zebrafish

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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