# Morphogenesis and growth of the ventricular wall in development and disease

> **NIH NIH P01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $2,386,125

## Abstract

ABSTRACT
Congenital heart defects (CHDs) are the most commonly encountered birth defect, affecting as many as 8 in
1,000 live births. In many cases, life-saving surgical intervention is required. Despite the prevalence, in many
cases the underlying molecular etiology of CHDs is not known. The central theme of this Program Project
Grant application is to elucidate mechanisms that regulate growth and morphogenesis of the ventricle during
development. Our objective is to gain understanding of how early events impacting mesoderm-lineage
specification and differentiation, how mid-gestational events impacting septation and papillary muscle
formation, and how late-gestational events impacting cardiomyocyte polarity and sarcomere maturation each
contribute to normal ventricular morphogenesis. Three highly interactive and complementary Projects are
proposed to attain these objectives. Project 1 will study the molecular mechanisms contributing to the genesis
of CHDs in an animal model of X-linked heterotaxy. These studies build on work from Dr. Stephanie Ware's
laboratory and will test the overall hypothesis that morphogenic defects in early embryonic structures can
impact the migration and differentiation of primitive progenitor cells which subsequently give rise to the
myocardium. Such a mechanism would explain why the spectrum of CHDs encountered in heterotaxia patients
is more severe than what would be anticipated to result from altered sidedness. Project 2 will study the
molecular mechanisms regulating ventricular septation and papillary muscle formation. These studies build on
work from Dr. Anthony Firulli's laboratory and will test the overall hypothesis that expression cardiomyogenic
transcription factors imparts morphogenic cues directing normal cardiomyocyte patterning in the developing left
ventricle, and that mid-gestational alteration of this patterning gives rise to CHD. Such a mechanism would
establish cell and molecular pathways which regulate normal and abnormal development of the ventricular
septation and papillary muscle. Project 3 will study the molecular mechanisms regulating compaction of the left
ventricle during cardiac development. These studies build on work from Dr. Weinian Shou's laboratory and will
test the overall hypothesis that altered cardiomyocyte cell polarity gives rise to ventricular noncompaction, and
furthermore, will dissect the molecular regulatory cascades which are required to establish normal
cardiomyocyte polarity. Such a mechanism would establish a common underlying molecular etiology which
gives rise to left ventricular noncompaction. The proposed work will be facilitated by the participation of three
cores (Administration, Cardiac Imaging and Mouse Resources). Ultimately, the studies proposed in this
Program Project Grant application will illustrate how events occurring prior to overt heart formation, during
early cardiac development, and during late maturation of the ventricular wall are sequentially integra...

## Key facts

- **NIH application ID:** 10111550
- **Project number:** 5P01HL134599-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Anthony B. Firulli
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,386,125
- **Award type:** 5
- **Project period:** 2017-02-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111550

## Citation

> US National Institutes of Health, RePORTER application 10111550, Morphogenesis and growth of the ventricular wall in development and disease (5P01HL134599-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10111550. Licensed CC0.

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