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

Lowe, Vanessa; Wisniewski, Laura; Sayers, Jacob; Evans, Ian; Frankel, Paul; Mercader-Huber, Nadia; Zachary, Ian C.; Pellet-Many, Caroline (2019). Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart. Development, 146(13) Company of Biologists Limited 10.1242/dev.174482

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy

UniBE Contributor:

Mercader Huber, Nadia Isabel

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0950-1991

Publisher:

Company of Biologists Limited

Language:

English

Submitter:

Nadia Isabel Mercader Huber

Date Deposited:

10 Dec 2019 14:59

Last Modified:

10 Dec 2019 15:09

Publisher DOI:

10.1242/dev.174482

PubMed ID:

31167777

BORIS DOI:

10.7892/boris.135529

URI:

https://boris.unibe.ch/id/eprint/135529

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