biostudies-literatureMiao LNEI NIH HHSAmerican Heart Association-American Stroke AssociationNHLBI NIH HHSNINDS NIH HHSNIAMS NIH HHSNIGMS NIH HHSeadd3417https://www.ebi.ac.uk/biostudies/studies/S-EPMC12662173biostudies-literatureUnknown387(6739)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 growthScience (New York, N.Y.)Tunneling nanotube-like structures regulate distant cellular interactions during heart formation.PMC12662173R01 HL121700R01 HL172834P30 EY007551R35 GM15317825EIA1422015R01 GM072804R01 GM143223R01 AR081487R21 NS138590Zheng YWu MLu YSchwartz RJSui HFan ZCSerysheva IIMiao LZhang SLiu YFan GZhao LWu CLGuo HZhou BHuyen TLNNusrat ABurns AREvans SMShou WKumar AWan LQfalseTunneling nanotube-like structures regulate distant cellular interactions during heart formation.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 growth2025-01-01T00:00:00Z2025 Mar2026-06-06T21:15:46.27Z2026-06-05T03:11:51.48ZS-EPMC126621734008058310.1126/science.add3417