# Molecular regulation of ventricular chamber maturation

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $407,826

## Abstract

Abstract
 Congenital heart diseases are the most common type of human birth defects, and many of these diseases
feature structural abnormalities that emerge during development. In order to meet an increasing physiological
demand of the growing embryo, the developing heart undergoes complex morphogenetic changes to optimize
its ventricular myoarchitecture for more efficient contraction. This proposal is focused on ventricular maturation
that is characterized by the formation of muscular protrusions called cardiac trabeculae. Our prior studies
revealed that cardiac trabeculation is initiated by directional cardiomyocyte migration from the compact layer,
and that ErbB2 cell-autonomously regulates this process. We also found that biomechanical forces generated
by the functioning embryonic heart is required for cardiac trabeculation. However, several outstanding questions
remain to be addressed, including those related to 1) the mechanism by which mechanical stimulus is sensed
and translated into spatial and temporal signals to regulate cardiac trabeculation and 2) the exact function of
cardiac trabeculae in the heart. It has been recognized that there exists an intimate relationship between cardiac
function and cardiac form. In this research program, we hypothesize that mechanical-biochemical interaction is
essential for cardiac trabecular formation and induces pathological hypertrophic remodeling in the absence of
trabecular formation. In support of this hypothesis, we found that primary cilia-mediated flow sensing is required
for trabeculation through activation of Notch signaling in the ventricular endocardium. While biomechanical forces
are required to initiate trabeculation, our preliminary study also revealed an essential role of cardiac trabeculae
in handling the mechanical forces generated by cardiac contraction. To test our hypothesis, we propose to further
delineate the mechanical-biochemical cellular signaling responsible for 1) trabecular formation, and 2) cardiac
dysfunction due to trabecular malformation. The successful completion of this proposal will not only define the
molecular and cellular mechanisms of ventricular maturation but also provide further mechanistic insight into the
inter-relationship between cardiac function and cardiac form.

## Key facts

- **NIH application ID:** 9858404
- **Project number:** 5R01HL139880-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jiandong Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $407,826
- **Award type:** 5
- **Project period:** 2018-02-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858404

## Citation

> US National Institutes of Health, RePORTER application 9858404, Molecular regulation of ventricular chamber maturation (5R01HL139880-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9858404. Licensed CC0.

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