Tunneling nanotube-like structures regulate distant cellular interactions during heart formation

• 成果类型: Article
• 署名作者: Miao, Lianjie; Lu, Yangyang; Nusrat, Anika; Fan, Guizhen; Zhang, Shaohua; Zhao, Luqi; Wu, Chia-Ling; Guo, Hongyan; Huyen, Trang Le Nu; Zheng, Yi; Fan, Zhen-Chuan; Shou, Weinian; Schwartz, Robert J.; Liu, Yu; Kumar, Ashok; Sui, Haixin; Serysheva, Irina I.; Burns, Alan R.; Wan, Leo Q.; Zhou, Bin; Evans, Sylvia M.; Wu, Mingfu
• 署名单位: University of Houston System; University of Houston; University of Texas System; University of Texas Health Science Center Houston; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Center for Excellence in Molecular Cell Science, CAS; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Zhejiang University; Zhejiang University; Indiana University System; Indiana University Bloomington; University of Houston System; University of Houston; Wadsworth Center; State University of New York (SUNY) System; State University of New York (SUNY) System; University at Albany, SUNY; University of Houston System; University of Houston; Rensselaer Polytechnic Institute; Rensselaer Polytechnic Institute; University of California System; University of California San Diego
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11963
• DOI: 10.1126/science.add3417
• 发表日期: 2025-03-14
• 关键词: receptor; notch; cytonemes; cdc42; morphogenesis; activation; neuregulin; ligand; cells; ephrin-b2

摘要

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.