# Mechanisms of signaling interaction between endocardium and myocardium

> **NIH NIH R01** · UNIVERSITY OF HOUSTON · 2024 · $675,606

## Abstract

Communication between the myocardium and endocardium, separated by a layer of cardiac jelly, is essential for
heart morphogenesis, especially trabecular formation. Trabeculae are sheet-like structures that increase surface
area when the coronary system is not yet established. Lack of trabeculation causes embryonic demise, and
excess trabeculation causes left ventricular noncompaction cardiomyopathy (LVNC). The mortality of patients
with LVNC ranges from 5% to 47%. Despite its clinical importance, the mechanisms of trabeculation are not fully
understood, and how the communication between cardiomyocytes (CMs) in the myocardium and endocardial
cells (ECs) in the endocardium is achieved and regulates trabeculation is not fully known.
Some ligands and receptors engaged in myocardium-endocardium communication are localized to membranes
of CMs and ECs, yet how ligand/receptor-mediated interactions occur across the cardiac jelly has yet to be
deciphered. Unlike direct cell-cell interactions, distant cell-cell communication can be achieved via several
mechanisms, including diffusible factors such as morphogens and recently discovered novel microstructures
such as tunneling nanotubes (TNTs) in cultured mammalian cells or cytonemes in flies. Whether a microstructure
that regulates signaling interaction among distant cells in vivo in mammals was not reported, and whether a
similar structure regulates the signaling interaction between the CMs and ECs during cardiovascular
morphogenesis is unknown. Via genetic labeling, electron microscopy (EM), and cryogenic-EM (Cryo-EM), our
preliminary data show a nanotube-like microstructure, which is named signaling bridges (SBs), extend from CMs
across cardiac jelly to reach ECs temporally; SB is sufficient to activate Notch signaling; disruption of SB by
deleting Cdc42 or by chemicals hinders Notch activation and alters CM cellular behaviors, resulting in
trabeculation defects. These novel preliminary data establish the essential roles of SBs in signal transduction
and trabeculation during cardiac morphogenesis; however, details regarding SB structure, function, and
regulatory mechanisms impacting heart morphogenesis remain unknown. We hypothesize that SBs are required
for the signaling interaction between the CMs and ECs to control cellular behaviors during trabeculation (Fig. 1).
Three aims are proposed: we will apply various electron microscopy to determine the ultrastructure and function
of SBs in Aim I; interrogate how SBs transduce signaling between ECs and CMs in Aim II; elucidate how SB
mediated interaction regulate trabecular morphogenesis in Aim III.
Completing the proposed studies will determine how signal interaction between the CMs and ECs is achieved
and how SBs regulate cellular behavior and trabecular formation. The discovery of SBs and their functions in
vivo opens new avenues for understanding intercellular interaction during cardiac morphogenesis. Successful
completion of this study will expand our un...

## Key facts

- **NIH application ID:** 10851367
- **Project number:** 1R01HL172834-01
- **Recipient organization:** UNIVERSITY OF HOUSTON
- **Principal Investigator:** Mingfu Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $675,606
- **Award type:** 1
- **Project period:** 2024-07-10 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851367

## Citation

> US National Institutes of Health, RePORTER application 10851367, Mechanisms of signaling interaction between endocardium and myocardium (1R01HL172834-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10851367. Licensed CC0.

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