期刊
DEVELOPMENT
卷 144, 期 8, 页码 1425-1440出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.143362
关键词
Heart regeneration; Endocardium; Myocardium; Signalling; Serpine1; Notch
资金
- Spanish Ministry of Economy, Industry and Competitiveness [Ministerio de Economia, Industria y Competitividad (MINECO)] [SAF2013-45543-R, RD12/0042/0005, RD12/0019/0003, CB16/11/00399]
- European Commission [FP7-ITN 215761, PITN-GA-2011-289600]
- MINECO
- Pro-CNIC Foundation
- 'Severo Ochoa' Center of Excellence (MINECO award) [SEV-2015-0505]
- Fonds Europeen de Developpement Regional (FEDER) funds
The zebrafish heart regenerates after ventricular damage through a process involving inflammation, fibrotic tissue deposition/removal and myocardial regeneration. Using 3D whole-mount imaging, we reveal a highly dynamic endocardium during cardiac regeneration, including changes in cell morphology, behaviour and gene expression. These events lay the foundation for an initial expansion of the endocardium that matures to form a coherent endocardial structure within the injury site. We studied two important endocardial molecules, Serpine1 and Notch, which are implicated in different aspects of endocardial regeneration. Notch signalling regulates developmental gene expression and features of endocardial maturation. Also, Notch manipulation interferes with attenuation of the inflammatory response and cardiomyocyte proliferation and dedifferentiation. serpine1 is strongly expressed very early in the wound endocardium, with decreasing expression at later time points. serpine1 expression persists in Notch-abrogated hearts, via what appears to be a conserved mechanism. Functional inhibition studies show that Serpine1 controls endocardial maturation and proliferation and cardiomyocyte proliferation. Thus, we describe a highly dynamic endocardium in the regenerating zebrafish heart, with two key endocardial players, Serpine1 and Notch signalling, regulating crucial regenerative processes.
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