# sox9b function in cardiomyocyte and great vessel development

> **NIH NIH P20** · OCEAN STATE RESEARCH INSTITUTE, INC. · 2021 · $53,252

## Abstract

PROJECT SUMMARY/ABSTRACT 
Congenital abnormalities of the heart and great vessels are the leading cause of infant mortality and morbidity 
in the United States yet the etiology of most congenital defects remains unknown. Approximately 90% of 
congenital heart and vessel defect cases are multifactorial. Exposure to environmental contaminants is thought 
to significantly contribute to the incidence of defects as well adult heart disease. Our long-term goal is to 
prevent and treat congenital defects and adult heart disease by understanding, in detail, the functions of genes 
that are critical for cardiovascular development and also disrupted by exposure to environmental toxicants. We 
have identified a candidate gene, SOX9, that is expressed in multiple cell types in the developing and mature 
heart and is downregulated in animal models following exposure to environmental toxicants present in air 
pollution, e-waste, plastics, and pesticides. Human mutations in the SOX9 coding region result in Campomelic 
Dysplasia (CD), a severe genetic disorder that usually results in death. A number of different congenital heart 
and great vessel defects have been reported in patients with CD as well as in individuals with mutations 
affecting SOX9 function. Together, the human loss of function data suggests that SOX9 plays several critical 
roles in cardiac and great vessel development. However, Sox9b/Sox9 functions in cardiomyocyte and great 
vessel development have not been investigated using animal models. Our preliminary data indicate that 
zebrafish Sox9b is essential for cardiomyocyte development and function as well as great vessel formation. 
Our immediate goal is to identify the molecular mechanisms that mediate the cardiac and great vessel 
phenotypes observed following loss of Sox9b function in zebrafish and to determine if Sox9b functions are 
conserved by mammalian Sox9. We are using an innovative multi-species approach and a combination of 
genetic tools to manipulate zebrafish Soxb and murine Sox9 during cardiovascular development. In Aim 1.1, 
we will determine if Sox9b is an inhibitor of canonical WNT signaling in the developing zebrafish heart. In Aim 
1.2, we will inhibit Sox9b function in embryonic cardiomyocytes and use RNAseq to identify additional 
molecular targets of Sox9b during zebrafish heart development. In Aim 2, we use the cell-type specific 
manipulations and optogenetics to determine how loss of Sox9b function leads to the great vessel phenotypes 
and to determine the relationship between Sox9b, Nkx2.5, and Stat4, two known mediators of great vessel 
development. In Aim 3, we will extend our understanding of Sox9b function in cardiac development by 
examining how loss of Sox9 in mouse cardiomyocytes and endothelial cells affects cardiac and great vessel 
development as well as how loss of Sox9 in the murine heart impacts canonical WNT signaling. Together, 
these studies will help us understand the endogenous functions of Sox9b/S...

## Key facts

- **NIH application ID:** 10200081
- **Project number:** 5P20GM103652-09
- **Recipient organization:** OCEAN STATE RESEARCH INSTITUTE, INC.
- **Principal Investigator:** Jessica Susan Plavicki
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $53,252
- **Award type:** 5
- **Project period:** 2013-09-20 → 2021-06-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200081

## Citation

> US National Institutes of Health, RePORTER application 10200081, sox9b function in cardiomyocyte and great vessel development (5P20GM103652-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200081. Licensed CC0.

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