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Updated: May 22, 2025

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

Lianjie Miao1, Yangyang Lu1, Anika Nusrat1

  • 1Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.

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|March 13, 2025
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Mammalian heart development involves direct cell communication via tunneling nanotube-like structures (TNTLs) connecting cardiomyocytes and endocardial cells. These TNTLs are crucial for signaling and forming ventricular trabeculae, with their loss disrupting cardiac patterning.

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Area of Science:

  • Developmental biology
  • Cardiovascular research
  • Cell biology

Background:

  • The developing mammalian heart relies on communication between the endocardium and myocardium, separated by cardiac jelly.
  • Mechanisms of intercellular communication across the cardiac jelly during cardiac morphogenesis remain unclear.

Purpose of the Study:

  • To investigate how membrane-localized receptors and ligands mediate interactions between the endocardium and myocardium during cardiac development.
  • To elucidate the role of specific microstructures in facilitating this communication.

Main Methods:

  • Utilized developing mouse cardiac morphogenesis models.
  • Employed a combination of cellular, imaging, and genetic approaches.
  • Investigated the structure and function of intercellular connections.

Main Results:

  • Identified tunneling nanotube-like structures (TNTLs) mediating direct interaction between cardiomyocytes (CMs) and endocardial cells (ECs).
  • Demonstrated that TNTLs transport cytoplasmic proteins and transduce signals between CMs and ECs.
  • Observed TNTLs initiating myocardial growth, contributing to ventricular trabeculae formation.

Conclusions:

  • TNTLs are a novel mechanism for direct intercellular communication across the cardiac jelly in the developing heart.
  • Disruption of TNTLs impairs essential signaling interactions, leading to defects in ventricular patterning.
  • These findings provide new insights into the cellular basis of cardiac morphogenesis.