# The Molecular regulation of ventricular compaction

> **NIH NIH P01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $472,653

## Abstract

ABSTRACT
Ventricular trabeculation and compaction are two distinct but related morphogenetic events that are essential for
normal ventricular myocardial wall development. Dysregulation of these events can lead to Left Ventricular
Noncompaction (LVNC, MIM300183 and 604169). LVNC is an inherited cardiomyopathy, and is clinically defined
by persistent LV trabeculae, increased inter-trabecular recesses, and thin LV walls, particularly at the apex.
LVNC is often associated with other congenital heart diseases (CHDs). The etiology and pathogenesis of LVNC
are elusive due to the genetic heterogeneity of the patients and the overall lack of understanding of the molecular
mechanisms orchestrating ventricular trabeculation and compaction. Previously, we have generated a number of
genetically modified mouse models which exhibit LVNC. Collectively these studies suggest a hypothesis wherein
Dishevelled-associated activator of morphogenesis 1 (Daam1) plays a key regulatory role in directing
compaction of the ventricular wall. Daam1 is an effector of non-canonical Wnt Planer Cell Polarity (PCP)
signaling and impacts actin polymerization, and Daam1 genetic ablation leads to ventricular noncompaction. We
hypothesized that Daam1-mediated signaling is critical to establish cardiomyocyte polarity, sarcomere
maturation, and through this process regulates ventricular wall compaction. Project 3 builds upon these findings
and will directly address the aforementioned hypothesis. Experiments proposed in Aim 1 will delineate the
molecular pathways which give rise to positive and negative regulation of Daam1 activity, and determine their
impact on ventricular wall compaction. Experiments proposed in Aim 2 will examine a number of additional
LVNC mouse models and test the hypothesis that Daam1-mediated loss of cardiomyocyte polarity constitutes a
common underlying molecular etiology for the genesis of LVNC. Collectively, the experiments proposed in
Project 3 will provide insight into how ventricular compaction is regulated, establishing novel understanding
of signaling pathways that when disrupted result in the pathogenesis of LVNC in mice and potentially in humans.

## Key facts

- **NIH application ID:** 10111570
- **Project number:** 5P01HL134599-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** WEINIAN SHOU
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $472,653
- **Award type:** 5
- **Project period:** 2017-02-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111570

## Citation

> US National Institutes of Health, RePORTER application 10111570, The Molecular regulation of ventricular compaction (5P01HL134599-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10111570. Licensed CC0.

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