# Molecular and cellular mechanisms causing cleft lip/palate

> **NIH NIH R01** · UNIVERSITY OF MISSOURI KANSAS CITY · 2020 · $559,527

## Abstract

Project Summary
Cleft lip with or without cleft palate (CLP) is one of the most common birth defects in man with an incidence of
between 1 in 700 and 1 in 1000 live births worldwide. Considerable progress has been made over the last few
decades to determine the genes responsible for syndromic forms of CLP and genome-wide association studies
have implicated many genomic regions (and candidate genes) in the genetic contribution to non-syndromic
CLP. However, for a substantial fraction of cleft cases, the underlying genetic basis remains unknown. In
addition, much of the focus on cleft gene functions has been on the few transcriptional regulators and growth
factors that have been implicated, largely ignoring the many other causative genes. He we pursue new findings
from two known CLP proteins, IRF6 and MID1, that suggest a convergence of function around the direct
regulation of epithelial cell-cell adhesion during lip morphogenesis. The project investigates the newly
discovered linkages that each of these proteins have with processes responsible for coordinating the dynamic
behavior of intercellular adhesion complexes with the underlying changes in the cellular cytoskeleton that
ultimately facilitate morphogenesis of the lip. In addition, we provide further support for the importance of
components of this specific regulatory complex by investigating the direct functional impact of likely pathogenic
variants recently discovered in a cohort of large multigenerational families with non-syndromic CLP. The
project is highlighted not just by the unique insight into the molecular mechanisms underlying CLP that the
research plan offers, but also the various novel and state-of-the-art approaches used to pursue the work aimed
at understanding the causes of this common birth defect.

## Key facts

- **NIH application ID:** 9880415
- **Project number:** 5R01DE027879-02
- **Recipient organization:** UNIVERSITY OF MISSOURI KANSAS CITY
- **Principal Investigator:** Timothy Chilton Cox
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $559,527
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880415

## Citation

> US National Institutes of Health, RePORTER application 9880415, Molecular and cellular mechanisms causing cleft lip/palate (5R01DE027879-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9880415. Licensed CC0.

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