title: PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts.
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.
authors.affiliation: Departments of Surgery and Pathology, Keck School of Medicine, University of Southern California, and The Saban Research Institute, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Zhang
authors.forename: Katie M
authors.initials: KM
authors.lastname: Wiens
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Nicole
authors.initials: N
authors.lastname: Rubin
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Robert I
authors.initials: RI
authors.lastname: Handin
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Chao
authors.forename: Tai-Lan
authors.initials: TL
authors.lastname: Tuan
authors.forename: Vaughn A
authors.initials: VA
authors.lastname: Starnes
authors.forename: Ching-Ling
authors.initials: CL
authors.lastname: Lien
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000033:anatomy & histology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010496:Pericardium / Q000166:cytology / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000033:anatomy & histology / Q000502:physiology
chemical_list: D015415:Biomarkers; D010982:Platelet-Derived Growth Factor