Mapping a fish's developing heart

By UdeMnouvelles
In 5 seconds High‑resolution imaging and genetics reveal the architecture and function of the coronary network of zebrafish, opening new avenues for understanding several congenital heart diseases.
Top left: This view of the zebrafish ventricle reveals the emergence of future coronary vessels, made visible through two fluorescent lines that label endothelial cells as they form. Bottom left: Using different fluorescent markers, this image simultaneously shows nascent coronary vessels, cardiomyocytes, and proliferating cells, illustrating the synchronized growth of the vascular network and the cardiac muscle. Bottom right: This view highlights the parallel progression of the developing coronary vessels and the growing cardiac muscle tissue, each marked with a distinct fluorescent color that allows their coordinated maturation to be followed.

Just in time for Heart Month, the laboratory of University de Montréal medical professor and CHU Sainte-Justine researcher Rubén Marín‑Juez has unveiled the first comprehensive atlas of coronary vessel development in the zebrafish. 

Led by PhD student Muhammad Abdul Rouf and the fruit of several years of meticulous analysis, this large‑scale work traces—with unprecedented single‑cell resolution—how vessels form and interact with the cardiac muscle.

Published in Development, the study combines 3D imaging with genetic zebrafish lines to determine where, when and how coronary vessels establish themselves and guide the maturation of cardiac muscle cells.

“For a long time, vessels were viewed simply as conduits that transport blood," Marín‑Juez, a researcher at CHU Sainte‑Justine's Azrieli Research Centre and professor in the university's Faculty of Medicine.

"Today, we show that the vessels orchestrate the growth of the cardiac muscle, starting from the earliest stages of heart formation," he said.

The idea for the research emerged from the lab’s work on cardiac regeneration: in adult zebrafish, coronary vessels form a kind of scaffold that enables the muscle to rebuild after an injury. This observation led the team to trace development back to the embryo to understand how these interactions arise from the very beginning of life.

Direct access to embryos

A model of choice in developmental biology, zebrafish develop a functioning heart just 24 hours after fertilization. With direct access to embryos and larvae—and cellular labeling made easier by their natural transparency—the Sainte-Justine research team observed structures that remain invisible in mammals at this early stage.

By analyzing vascular development micrometre by micrometre, starting at a body length of 7 millimetres, the team produced remarkably precise 3D images. This approach made it possible to follow the formation of the coronary network: the emergence of the first vascular sprouts, their anchoring, growth, branching and maturation into a fully functional network.

Comparing different zebrafish models also revealed the exact moment when development goes awry, highlighting defects that arise when a key gene is altered.

In parallel, the team performed RNA sequencing on more than 37,000 cells, identifying the various types involved, as well as new markers and molecular signatures associated with key stages of coronary development. The atlas thus offers a complete anatomical and genomic portrait of how the coronary network takes shape.

Opens new avenues

Beyond fundamental insights, the atlas also opens new avenues for understanding several congenital heart diseases. 

Increasing evidence suggests that an insufficient or disorganized coronary network very early in development can compromise normal heart formation. By mapping these steps with such precision, the study now enables researchers to explore these hypotheses much further.

In species capable of regenerating their hearts, such as zebrafish, several developmental programs are reactivated after injury. Understanding these mechanisms at the embryonic stage could therefore inspire future therapeutic approaches, particularly in pediatrics.

By combining cutting‑edge imaging, genetics and single‑cell analyses, this study highlights the strength of collaboration between scientific teams and technological platforms—a partnership that is transforming our understanding of the heart from its very first beats, the scientists say.

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