# Cellular and Molecular Analysis of Body Wall Closure

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2021 · $194,375

## Abstract

Mammalian ventral body wall closure defects, including gastroschisis, thoracoabdominoschisis, and
omphalocele are linked with the morphogenesis of the ventral body wall, the amnion, and the umbilical ring.
Malformations of the ventral body wall comprise one of the leading categories of human birth defects and are
present in about one out of every 2000 live births. Although the occurrence of these defects is relatively
common, there is a surprising lack of knowldege concerning the development and closure of the ventral body
wall in mouse or human. This field is further complicated by the array of theories on the pathogenesis of
human body wall defects that have not been experimentally tested. This proposal aims to produce a paradigm
shift in our understanding of mammalian ventral body closure that can provide a mechanistic framework and
comprehensive resource for future understanding of how this process goes awry because of genetic and/or
environmental causes. The transcription factor AP-2, encoded by the gene Tfap2a, has an essential role in
mouse body wall closure and previous studies have shown that it regulates ectodermal, mesenchymal,
peripheral nervous system, and mesodermal interactions that drive development of the ventral body wall.
Tfap2a null mice have a severe form of ventral closure defect, a thoracoabdominoschisis, in which the ventral
covering of the chest and abdomen fails to form so that the heart, lungs, liver, and gut are exposed. Critically,
this is one of the few simple mouse models that gives a fully penetrant and consistent body wall closure defect
that can be used to understand how this important developmental process can fail. In the first Aim, relevant
tissue will be collected from control and Tfap2a null mice at specific embryonic times and subjected to single
cell RNA seq (scRNAseq) analysis. This will identify the normal gene expression patterns of mouse body wall
closure as well as cell types and genes that are impacted by loss of Tfap2a. Several additional genes are
known to affect body wall closure and we will be able to attribute these genes to relevant tissue populations to
understand how they may be influencing this critical developmental process. In the second Aim, we will
perform scATACseq analysis on all control time points as well as the most relevant time points for the mutant.
We will then integrate all the scRNAseq and scATACseq data to identify the tissues, cell types, and gene
expression signatures that are normally associated with body wall closure. Further, we will identify how
chromatin accessibility in the body wall is altered by loss of Tfap2a. Verification analyses will be performed to
identify critical changes in cell populations and gene expression profiles associated with normal and abnormal
body wall closure. Subsequently, the information from these studies will be synthesised into a novel and
powerful model for normal body wall closure that can serve as an important framework for future under...

## Key facts

- **NIH application ID:** 10133115
- **Project number:** 5R21HD099546-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** TREVOR J WILLIAMS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2020-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133115

## Citation

> US National Institutes of Health, RePORTER application 10133115, Cellular and Molecular Analysis of Body Wall Closure (5R21HD099546-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133115. Licensed CC0.

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