PUBLICATION

PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts

Authors

Kim, J., Wu, Q., Zhang, Y., Wiens, K.M., Huang, Y., Rubin, N., Shimada, H., Handin, R.I., Chao, M.Y., Tuan, T.L., Starnes, V.A., and Lien, C.L.

ID

ZDB-PUB-101004-32

Date

2010

Source

Proceedings of the National Academy of Sciences of the United States of America 107(40): 17206-17210 (Journal)

Registered Authors

Handin, Robert, Lien, Ching-Ling (Ellen)

Keywords

epicardium, mesenchymal cells, mural cells, zebrafish heart regeneration

MeSH Terms

Signal Transduction/physiology*
Neovascularization, Physiologic/physiology*
Heart*/anatomy & histology
Heart*/physiology
Blood Vessels/anatomy & histology
Blood Vessels/physiology*
Cell Differentiation/physiology
Regeneration/physiology*
Zebrafish*/anatomy & histology
Zebrafish*/physiology
Animals
Platelet-Derived Growth Factor/metabolism*
Biomarkers/metabolism
Pericardium/cytology
Pericardium/physiology

(all 15)

PubMed

20858732 Full text @ Proc. Natl. Acad. Sci. USA

Abstract

A zebrafish heart can fully regenerate after amputation of up to 20% of its ventricle. During this process, newly formed coronary blood vessels revascularize the regenerating tissue. The formation of coronary blood vessels during zebrafish heart regeneration likely recapitulates embryonic coronary vessel development, which involves the activation and proliferation of the epicardium, followed by an epithelial-to-mesenchymal transition. The molecular and cellular mechanisms underlying these processes are not well understood. We examined the role of PDGF signaling in explant-derived primary cultured epicardial cells in vitro and in regenerating zebrafish hearts in vivo. We observed that mural and mesenchymal cell markers, including pdgfrβ, are up-regulated in the regenerating hearts. Using a primary culture of epicardial cells derived from heart explants, we found that PDGF signaling is essential for epicardial cell proliferation. PDGF also induces stress fibers and loss of cell-cell contacts of epicardial cells in explant culture. This effect is mediated by Rho-associated protein kinase. Inhibition of PDGF signaling in vivo impairs epicardial cell proliferation, expression of mesenchymal and mural cell markers, and coronary blood vessel formation. Our data suggest that PDGF signaling plays important roles in epicardial function and coronary vessel formation during heart regeneration in zebrafish.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
acta2	WT	physical alteration: anatomical structure	Adult		cardiac ventricle regenerating tissue	ISH	Fig. 2
acta2	WT	physical alteration: anatomical structure, chemical treatment: dimethyl sulfoxide	Adult		cardiac ventricle regenerating tissue	ISH	Fig. 5
acta2	WT	physical alteration: anatomical structure, chemical treatment: pharmaceutical	Adult		cardiac ventricle regenerating tissue	ISH	Fig. 5
acta2	WT	control	Adult	Not Detected	cardiac ventricle	ISH	Fig. 2
EGFP	la2Tg	physical alteration: anatomical structure	Adult		thrombocyte	IFL	Fig. S2
EGFP	y1Tg	physical alteration: anatomical structure, chemical treatment: pharmaceutical	Adult	Not Detected	cardiac ventricle regenerating tissue	IFL	Fig. 5
EGFP	y1Tg	physical alteration: anatomical structure, chemical treatment: dimethyl sulfoxide	Adult		cardiac ventricle regenerating tissue	IFL	Fig. 5
pdgfra	WT	physical alteration: anatomical structure	Adult		cardiac ventricle regenerating tissue	ISH	Fig. 3
pdgfra	WT	control	Adult	Not Detected	cardiac ventricle	ISH	Fig. 3
pdgfrb	WT	physical alteration: anatomical structure	Adult		cardiac ventricle regenerating tissue	ISH	Fig. 3

1 - 10 of 30

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
y1Tg	physical alteration: anatomical structure, chemical treatment: pharmaceutical	Adult	regenerating tissue blood vessel aplastic, abnormal	Fig. 5
y1Tg	physical alteration: anatomical structure, chemical treatment: pharmaceutical	Adult	regenerating tissue endothelial cell absent, abnormal	Fig. 5
y1Tg	physical alteration: anatomical structure, chemical treatment: pharmaceutical	Adult	tissue regeneration disrupted, abnormal	Fig. 5

1 - 3 of 3

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
la2Tg	Tg(-6.0itga2b:EGFP)	Transgenic Insertion
y1Tg	Tg(fli1:EGFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
la2Tg
WT
y1Tg

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-pdgfb	polyclonal			Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Kim et al., 2010 ZDB-PUB-101004-32 PMID:20858732

PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts

Kim et al., 2010

ZDB-PUB-101004-32
PMID:20858732