Regenerating vascular mural cells in zebrafish fin blood vessels are not derived from pre-existing mural cells and differentially require Pdgfrb signalling for their development

Author:

Leonard Elvin V.12,Figueroa Ricardo J.3,Bussmann Jeroen14,Lawson Nathan D.5ORCID,Amigo Julio D.3,Siekmann Arndt F.12ORCID

Affiliation:

1. Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149 Münster, Germany

2. Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, 1114 Biomedical Research Building, 421 Curie Boulevard, Philadelphia, PA 19104, USA

3. Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile

4. Division of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands

5. Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA

Abstract

ABSTRACT Vascular networks comprise endothelial cells and mural cells, which include pericytes and smooth muscle cells. To elucidate the mechanisms controlling mural cell recruitment during development and tissue regeneration, we studied zebrafish caudal fin arteries. Mural cells colonizing arteries proximal to the body wrapped around them, whereas those in more distal regions extended protrusions along the proximo-distal vascular axis. Both cell populations expressed platelet-derived growth factor receptor β (pdgfrb) and the smooth muscle cell marker myosin heavy chain 11a (myh11a). Most wrapping cells in proximal locations additionally expressed actin alpha2, smooth muscle (acta2). Loss of Pdgfrb signalling specifically decreased mural cell numbers at the vascular front. Using lineage tracing, we demonstrate that precursor cells located in periarterial regions and expressing Pgdfrb can give rise to mural cells. Studying tissue regeneration, we did not find evidence that newly formed mural cells were derived from pre-existing cells. Together, our findings reveal conserved roles for Pdgfrb signalling in development and regeneration, and suggest a limited capacity of mural cells to self-renew or contribute to other cell types during tissue regeneration.

Funder

Bundesministerium für Bildung und Forschung

Deutsche Forschungsgemeinschaft

National Heart, Lung and Blood Institute

University of Münster

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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