Border-zone cardiomyocytes and macrophages regulate extracellular matrix remodeling to promote cardiomyocyte protrusion during cardiac regeneration.
We provide a comprehensive characterization of CM protrusion and invasion during zebrafish cardiac regeneration using histological and time-lapse imaging approaches. Further, using genetic and clodronate ablation models, we provide evidence that macrophage presence at the border zone of regenerating hearts is essential for ECM remodeling and subsequent CM invasion. We show that Mmp14b plays an important role in macrophage presence and ECM remodeling at the border zone and subsequent CM invasion. Lastly, we also show that CM-specific mmp14b OE is sufficient to promote CM invasion in vivo.
Constanty F*, Wu B*, Wei KH, Lin IT, Dallmann J, Guenther S, Lautenschlaeger T, Priya R, Lai SL, Stainier DYR, Beisaw A. Border-zone cardiomyocytes and macrophages regulate extracellular matrix remodeling to promote cardiomyocyte protrusion during cardiac regeneration. Nature Communications 2025; 16: 3828 doi:10.1038/s41467-025-59169-4 *co-first authors