# Gene Regulatory Networks for Cardiac Morphogenesis

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $619,485

## Abstract

Abstract
Congenital Heart Disease (CHD), malformations of the heart present at birth, is the most
common class of life-threatening birth defect. Atrioventricular Septal Defects (AVSDs) are a
common and serious form of CHD in humans, comprising 5-10% of all CHD and a greater
proportion of cases requiring surgical intervention. Gaining a mechanistic understanding of
atrioventricular (AV) septation is an essential goal for improving clinical approaches to structural
heart disease.
This R01 is based on a paradigm shift in the understanding of AV septation. Whereas the
canonical view of AV septation was based on intracardiac events centered at the endocardial
cushion, recent work demonstrated that the T-box transcription factor Tbx5 is required in the
Second Heart Field, outside of the heart proper, for AV septation. In this proposal, we harness
this new understanding of AV septation to address the molecular and biochemical mechanisms
underlying AV septation, using Tbx5 as an entry point. We propose to (1) define the molecular
basis of TBX5 regulation of Wnt2, required for lung development and thereby AV septation, (2)
identify the proteins that interact with and function with Tbx5 in the SHF for AV septation; and
(3) define the biochemical mechanisms underlying the function of Tbx5 in the SHF.
The ultimate aim of the proposed work is to understand the molecular and biochemical basis of
AV septation. This proposal will increase understanding of the molecular ontogeny of human
AVSDs. This work is an essential step towards defining the causes of human CHD and
improving the natural history of patients with CHD.

## Key facts

- **NIH application ID:** 9889169
- **Project number:** 5R01HL126509-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Frank Leo Conlon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $619,485
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889169

## Citation

> US National Institutes of Health, RePORTER application 9889169, Gene Regulatory Networks for Cardiac Morphogenesis (5R01HL126509-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9889169. Licensed CC0.

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