# Signaling control and cellular basis of craniofacial morphogenesis and congenital disease

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $1,021,044

## Abstract

Project Summary
Congenital craniofacial anomalies are common and arise from cellular changes that cause aberrant tissue-level
alterations in shape. Though significant understanding of the gene regulatory networks that pattern craniofacial
development has been achieved, knowledge regarding the cellular and physical processes driving craniofacial
morphogenesis lags behind. A particular paucity of information exists on the cellular changes that drive specific
craniofacial dysmorphologies. In recent years, my laboratory has assembled a battery of tools and established
a network of collaborations to address the signaling control of physical aspects of morphogenesis. By generating
new live imaging platforms for the study of lip and secondary palate fusion, we have identified novel cellular
behaviors that contribute to this process. We have pursued a detailed understanding of the cellular mechanisms
of craniofrontonasal syndrome, a condition that we have learned results from aberrant cell segregation behavior
and resultant changes in tissue shape. We have established the first hiPSC model of a craniofacial condition,
allowing us to address questions of cellular morphogenesis in a human system for the first time. Here we propose
a series of new directions that focus on the cellular basis of craniofacial morphogenesis and how it goes wrong
in congenital craniofacial conditions. These include three main goals: 1) Understand the control of mesenchymal
cell movement in shaping craniofacial tissues 2) Elucidate mechanisms of craniofacial epithelial tissue fusion at
cellular and molecular resolution 3) Elaborate novel regulators of mammalian craniofacial morphogenesis by use
of cutting edge CRISPR/Cas9 methodology in a human craniofacial disease-biased mutagenesis approach.
Achieving these goals will drive understanding of basic principles of cellular morphogenesis in craniofacial
development and increasingly provide opportunities to adapt these principles toward therapeutic and tissue
engineering approaches to treat congenital craniofacial anomalies.

## Key facts

- **NIH application ID:** 10798224
- **Project number:** 5R35DE031926-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jeffrey Ohmann Bush
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,021,044
- **Award type:** 5
- **Project period:** 2022-04-01 → 2030-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798224

## Citation

> US National Institutes of Health, RePORTER application 10798224, Signaling control and cellular basis of craniofacial morphogenesis and congenital disease (5R35DE031926-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10798224. Licensed CC0.

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