The zebrafish cardiovascular system. Representation of key elements of the zebrafish cardiovascular anatomy in embryonic/larval (A–D) and adult (E–H) stages. (A) Schematic overview of the circulatory system in a zebrafish embryo, showing the location of images in panels C and D. bottom: angiogram of a 5 days post fertilization (dpf) Tg(gata1:dsRed) zebrafish embryo, showing the trajectory of fluorescent erythrocytes throughout the circulation. (B) Schematic representation of the zebrafish embryo heart, with indication of blood flow direction (arrows). (C) Lateral view of trunk blood vessels in a 2dpf Tg(kdrl:ras-mCherry;fli1a:nls-gfp) zebrafish embryo, with endothelial cell membranes in magenta and endothelial cell nuclei in green. (D) Ventral view of the head of a Tg(kdrl:egfp) 4 dpf zebrafish larva, showing the heart and outflow tract. (E) Schematic overview of the adult zebrafish heart. The approximate planes of the cardiac sections in panels (F) and (G) are indicated with a dotted line. (F–H) Resorcin-fuchsin stain of elastin fibers (dark purple to black) in sections of a 9-month-old male zebrafish. (F,G) cardiac chambers and valves, (H) cross-section of the ventral aorta. AA, aortic arches; A, atrium; AV, atrioventricular valve; BA, bulbus arteriosus; BrA, branchial arteries; BV, bulboventricular valve; DA, dorsal aorta; DLAV, dorsal longitudinal anostomotic vessels; G, gills; ISV, intersegmental vessel; PCV, posterior caudal vein; V, ventricle; VA, ventral aorta. Created in BioRender. Sips, P. (2025) https://BioRender.com/z89q283.

Aortic hemorrhage in a zebrafish larva. Brightfield image of a 6 days post fertilization (dpf) col5a1-depleted larva (CRISPR/Cas9-injected, F0 generation), showing evidence of blood pooling near the dorsal aorta (red arrow). Adapted with permission from “Knocking out Ehlers-Danlos and Marfan Syndrome-related genes generates vascular phenotypes.” by Andrew Prendergast, Bulat A. Ziganshin, Dimitra Papanikolaou, Mohammad A. Zafar, Stefania Nicoli, Sandip Mukherjee and John A. Elefteriades, licensed under CC BY 4.0.

Overview of zebrafish strategies for the modeling of variants in genes associated with TAAD. Several different strategies are currently available for gene and variant testing in zebrafish. Each approach has specific advantages and disadvantages, rendering it more or less suitable for various purposes. Depending on the chosen strategy, phenotyping of the zebrafish can be performed in embryonic and larval stages, or also at later ages. Created in BioRender. Sips, P. (2025) https://BioRender.com/z58k940.