Researchers identify a cell layer needed for zebrafish heart growth; other cells rebuild muscle after injury

Researchers identify a cell layer needed for zebrafish heart growth; other cells rebuild muscle after injury

In an eLife article published on September 8, biologists described a thin layer of cardiomyocytes, the muscle cells that contract the heart, in zebrafish. During growth, this layer helps form the heart’s muscular wall and the coronary vessels that supply it. After the tip of the ventricle is removed, other cardiomyocytes replace the lost tissue.

The zebrafish heart can regrow lost muscle after injury. Surviving cardiomyocytes change their state, divide, and replace the missing tissue. These cells form several layers in the heart. The authors examined the role of one of these layers.

They first mapped 1 668 cardiomyocytes from adult hearts and identified a group in which the gene phlda2 was active. These cells form a thin layer between the outer compact muscle and the inner trabeculae, which are muscular bridges. The researchers then generated a zebrafish line in which cells with active phlda2 produce the bacterial enzyme NTR, making them sensitive to metronidazole. Treatment eliminated about 96,9% of these cells from the ventricle.

In young fish, the area of trabecular muscle decreased by approximately 54,7%, the outer compact layer became disorganized, and the coronary vessels fragmented. The vascular pattern remained disrupted after 90 days. These findings indicate that this layer contributes to the formation of muscle and the vascular network as the heart grows.

In adult fish, the researchers removed the tip of the ventricle six days after treatment began. A week later, the wound contained as many cells with active gata4 as wounds in control fish. This gene is activated in dividing cardiomyocytes during regeneration. By day 30, new muscle covered the injured area; vessel density and scar area also matched those in controls.

The layer with active phlda2 itself had not regenerated in the wound even after 60 days. Its cells were distinct from those that activated gata4 during regeneration. In this experiment, different cardiomyocyte populations supported heart growth and the repair of adult tissue.