# Integrated multi-omics analyses of early mammalian craniofacial development

> **NIH NIH R03** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $164,000

## Abstract

Abstract
Craniofacial abnormalities are some of the most commonly occurring human birth defects worldwide,
with up to 200,000 children born every year with some type of craniofacial defect. These defects can
occur as part of complex syndromes that involve multiple tissues and organs. The syndromic forms of
these disorders have been successfully linked to nearly 500 genes including TWIST1 for
craniosynostosis and IRF6 for orofacial clefting. However more frequently no other part of the body is
directly involved (50% of craniosynostoses, 70% of orofacial clefts). Genome wide association studies
indicate heritability for such defects, however the vast majority of associations fall outside of genes
suggesting defective gene regulation is a major contributor to incidence of such defects. Gene
regulatory elements can be located throughout the genome and typically have tissue-specific activity,
making them difficult to identify and predict what gene they control. The overall objective of this
application is to integrate epigenomic and transcriptomic data sets from early human and mouse
craniofacial development from our lab as well as FaceBase to comprehensively predict regulatory
element-gene interactions. Our hypothesis posits that conserved regulatory networks between
human and mouse are enriched for disease relevant biology. In Aim 1 we propose to
systematically identify chromatin states in human from 4.5 to 8 weeks of gestation and in mouse from
embryonic days 9.5 to 15.5. In Aim 2 we propose to identify genes that are coordinately regulated in
both species across these developmental windows. Finally, in Aim 3 we propose to integrate these two
disparate network types to identify regulatory element-gene pairings. We will experimentally validate
predicted interactions in a culture model of cranial neural crest cells using proximity-ligation coupled
with immunoprecipitation. Our proposed studies will generate the most comprehensive epigenomic
and transcriptomic networks in a developing human tissue and for the first time identify the conserved
regulatory architecture for building the mammalian orofacial complex.

## Key facts

- **NIH application ID:** 10083207
- **Project number:** 5R03DE028588-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Justin Lee Cotney
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $164,000
- **Award type:** 5
- **Project period:** 2020-01-08 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083207

## Citation

> US National Institutes of Health, RePORTER application 10083207, Integrated multi-omics analyses of early mammalian craniofacial development (5R03DE028588-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10083207. Licensed CC0.

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