Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

Notch signalling restricts inflammation and serpine1 in the dynamic endocardium of the regenerating zebrafish heart


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 the 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, in 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 heart and two key endocardial players, Serpine1 and Notch signalling, regulating crucial regenerative processes.

Type Journal
ISBN 1477-9129 (Electronic) 0950-1991 (Linking)
Authors Munch, J.; Grivas, D.; Gonzalez-Rajal, A.; Torregrosa-Carrion, R.; de la Pompa, J. L.
Responsible Garvan Author Dr Alvaro Gonzalez Rajal
Publisher Name DEVELOPMENT
Published Date 2017-04-15
Published Volume 144
Published Issue 8
Published Pages 1425-1440
Status Published in-print
DOI 10.1242/dev.143362
URL link to publisher's version
OpenAccess link to author's accepted manuscript version