Tunneling nanotube–like structures regulate distant cellular interactions during heart formation
Lianjie Miao, Yangyang Lu, Anika Nusrat, Guizhen Fan, Shaohua Zhang, Luqi Zhao, Chia‐Ling Wu, Hongyan Guo, Tran Bang Huyen, Yi Zheng, Zhen‐Chuan Fan, Weinian Shou, Robert J. Schwartz, Yu Liu, Ashok Kumar, Haixin Sui, Irina I. Serysheva, Alan R. Burns, Leo Q. Wan, Bin Zhou, Sylvia Μ. Evans, Mingfu Wu
Abstract
In the developing mammalian heart, the endocardium and the myocardium are separated by so-called cardiac jelly. Communication between the endocardium and the myocardium is essential for cardiac morphogenesis. How membrane-localized receptors and ligands achieve interaction across the cardiac jelly is not understood. Working in developing mouse cardiac morphogenesis models, we used a variety of cellular, imaging, and genetic approaches to elucidate this question. We found that myocardium and endocardium interacted directly through microstructures termed tunneling nanotube-like structures (TNTLs). TNTLs extended from cardiomyocytes (CMs) to contact endocardial cells (ECs) directly. TNTLs transported cytoplasmic proteins, transduced signals between CMs and ECs, and initiated myocardial growth toward the heart lumen to form ventricular trabeculae-like structures. Loss of TNTLs disturbed signaling interactions and, subsequently, ventricular patterning.