Reviewed by Lexie CornerMar 18 2025
Researchers at the University of Houston have provided new insights into the basic process of heart development in utero, offering potential advancements in the treatment of heart disease. The study focuses on tunneling nanotube-like structures, which are long, thin membrane channels that connect cells. The research was published in Science.
Images of tunneling nanotubes. Arrows pointing to the tunneling nanotubes. Tunneling nanotubes in immune cells, CC BY 4.0, Confocal image of day 13 HIV-1-infected human monocyte-derived macrophages and MGC interconnected through a TNT. Arrowheads show a TNT. HIV-1 Gag (red), F-actin (green), DAPI (blue). Scale bar, 50 µm. Image Credit: Dupont M., Wikimedia Commons.
Mingfu Wu, an Associate Professor and member of the Drug Discovery Institute, contributed to the study. Wu explained that these structures may represent a fundamental mechanism for cell communication, offering new insights into the development of cardiac diseases and potential treatments.
The myocardium, the muscle responsible for the heartbeat, and the endocardium, the inner lining of the heart, exchange critical signals essential for heart formation. This connection is necessary for proper heart development and function.
Here, we characterized Tunneling Nanotube-Like Structures (TNTLs), which we found physically connecting cardiomyocytes in myocardium to endocardial cells in endocardium.
Mingfu Wu, Associate Professor and Member, Drug Discovery Institute, College of Pharmacy, University of Houston
“These structures likely help to facilitate long-distance intercellular communication essential for heart formation,” said Lianjie Miao, Research Assistant Professor of Pharmacology and the Study’s First Author.
The signals are particularly important during the growth of the trabeculae, which is crucial for the early development of the heart. Trabeculae increase the inner surface area of the heart wall, facilitating blood circulation before the coronary system develops, and enhancing nutrient and oxygen exchange between the heart wall and the blood.
Wu and the team confirmed the presence of tunneling nanotubes in embryonic hearts through genetic labeling, contact tracing, and advanced imaging techniques. They found that these tubes extended across the cardiac jelly and major heart layers, forming direct connections that enable cells to exchange proteins and interact, performing essential functions.
“We found that TNTLs were able to transport signaling molecules, cytoplasmic proteins, and trafficking vesicles, underscoring their role as conduits for intercellular communication and proving them essential in cardiac morphogenesis,” said Wu.
Disruption of TNTLs in embryonic hearts resulted in impaired ventricular wall morphogenesis, evidenced by loss of trabeculae and defective myocardial growth.
Mingfu Wu, Associate Professor and Member, Drug Discovery Institute, College of Pharmacy, University of Houston
Wu stated that future studies should examine the molecular mechanisms that control the formation of TNTLs, the possible roles of protein transfer between the myocardium and endocardium during the formation of the heart, and how altering or regulating these structures may result in novel treatments for heart failure and congenital cardiac defects.
Journal Reference:
Miao, L., et al. (2025) Tunneling nanotube–like structures regulate distant cellular interactions during heart formation. Science. doi.org/10.1126/science.add3417