Cleft palate is among the most common craniofacial malformations, affecting one in every 1000 live births worldwide. Cleft palate can be a part of genetic syndromes and also can occur as an isolated or non-syndromic birth defect. Non-syndromic cleft palate is a complex trait and can be due to genetic abnormalities, environmental influences or the combination of both that disturb secondary palate development. The mammalian secondary palate is formed by fusion of two separate palatal shelves that are derived from the maxillary processes. After initial vertical growth on either side of the tongue, the palatal shelves undergo an elevation process and move into a horizontal position above the tongue where the opposing shelves approximate each other for contact and fusion. Failure or delay of palatal shelf elevation is a common cause of cleft palate. In this application, we will develop new experimental approaches to validate different models of palatal shelf elevation and to further elucidate the mechanism of palatal shelf elevation. We propose two specific aims for this research project: 1) to determine if palatal shelf elevation results from shelf mechanical rotation or from shelf shape changes or remodeling; 2) to determine the role of hyaluronic acid in palatal morphogenesis. To achieve these aims, we will combine ex vivo shelf elevation with dye labeling of palatal cells to examine shelf elevation behaviors and use the mouse genetic approach to study the function of mesenchymal hyaluronic acid during palatal shelf elevation. The results of these studies will refine and improve our knowledge on palate development and pathogenesis of cleft palate, which is important for developing methods that could promote palatal shelf elevation and reduce chances of cleft palate formation.

Public Health Relevance

Cleft palate is one of the most common birth defects, which results from failure of closure of the secondary palate during gestation. This research project aims to develop new approaches for studying the role of hyaluronic acid in regulating morphogenesis during secondary palate closure, a key step of palatogenesis that is vulnerable to various genetic and environmental risk factors. The results of this study will significantly advance our understanding of the mechanism of palate development and cleft palate formation, which would aid in developing new strategies for prevention, diagnosis and treatment of cleft palate disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
5R03DE025077-02
Application #
9185968
Study Section
NIDR Special Grants Review Committee (DSR)
Program Officer
Scholnick, Steven
Project Start
2016-01-01
Project End
2017-12-31
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98101