# Investigating the role of Yap/Taz in neural crest-derived cardiac development

> **NIH NIH F31** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $37,124

## Abstract

Project Summary/Abstract
Congenital heart defects (CHDs) are the most common human birth defect. Although CHDs are highly
prevalent, knowledge regarding disease onset is currently limited, restricting therapeutic progression. CHDs
can arise due to the altered contribution of cardiac progenitor cell populations, including cardiac neural crest
cells (NCCs), a vital migratory and multipotent cell population for proper mammalian heart formation. The
fundamental Hippo signaling pathway is crucial in regulating heart development and homeostasis. Patient data
and animal models have indicated that changes in Hippo signaling result in various types of CHDs. The
canonical Hippo downstream effectors Yap and Taz are essential for NCC regulation throughout the developing
embryo, yet their role in NCC-derived heart development remains unknown. I maintain a mouse cohort with a
Cre recombinase conditional deletion of Yap/Taz in the NCC population and found that Yap/Taz deficiencies in
NCCs result in external and internal cardiac defects, creating a CHD mouse model. Furthermore, I identified
that deficiencies of Yap/Taz reduced cardiac outflow tract (OFT) cell migration capabilities ex vivo and in vitro.
This project aims to define how mutant Hippo signaling drives the dysregulation of NC and cardiac
development. I hypothesize that the Hippo signaling effectors Yap/Taz regulate proper cardiac remodeling
during NCC-derived heart development. Aim 1 will investigate the role of Yap/Taz in cardiac OFT development
by characterizing altered cellular composition due to Yap/Taz deficiencies and performing sc-multi-omics on
control and Yap/Taz deficient cardiac OFTs. Aim 2 will explore the mechanism underlying Hippo-regulated NCC
differentiation and its impact on cardiac tissue stiffness both in vivo and in vitro. This project will elucidate the
roles of Hippo signaling in NCC-derived heart development. Findings from these proposed studies will shed
light on the molecular mechanisms regulating heart development and help develop novel diagnostic and
therapeutic strategies for CHDs.

## Key facts

- **NIH application ID:** 10999063
- **Project number:** 1F31HL176166-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Shannon Nicole Erhardt
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $37,124
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10999063

## Citation

> US National Institutes of Health, RePORTER application 10999063, Investigating the role of Yap/Taz in neural crest-derived cardiac development (1F31HL176166-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10999063. Licensed CC0.

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