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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, IC; (2019) Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart. Development 10.1242/dev.174482. (In press). Green open access

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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.

Type: Article
Title: Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.174482
Publisher version: https://doi.org/10.1242/dev.174482
Language: English
Additional information: © 2019. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Epicardium, Heart, Neuropilin, Regeneration, Zebrafish
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/10076197
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