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

BioRxiv : the Preprint Server for Biology
Vanessa LoweCaroline Pellet-Many

Abstract

Unlike adult mammals, zebrafish are able to naturally regenerate their heart. A key mechanism in zebrafish heart regeneration is the activation of the epicardium, leading to the establishment of a supporting scaffold for newly formed cardiomyocytes, angiogenesis and cytokine secretion. Neuropilins (NRPs) are cell surface co-receptors mediating functional signaling of kinase receptors for cytokines known to play critical roles in zebrafish heart regeneration, including Platelet-Derived growth factor (PDGF), Vascular Endothelial growth factor (VEGF), and Fibroblast growth factor (FGF). Herein, we investigated the role of neuropilins in the response of the zebrafish heart to injury and its subsequent regeneration. All four zebrafish neuropilin isoforms, nrp1a, 1b, 2a, and 2b, were upregulated following cardiac cryoinjury and were strongly expressed by the activated epicardium. A nrp1a mutant, coding for a truncated, non-functional protein, showed a significant delay in heart regeneration in comparison to Wild-Type fish 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 Wilms tumor 1 was sever...Continue Reading

Related Concepts

Chemically Induced
Collagen
Growth Factor
Heart
Medical Devices
Nephroblastoma
Platelet-Derived Growth Factor
Natural Regeneration
Up-Regulation (Physiology)
Zebrafish

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