Cleft lip and palate are common congenital anomalies that can arise from defects in tissue fusion, a process in which two independent prominences become one continuous structure. Tissue fusion is common across multiple contexts during development, including neural tube closure, heart, and urogenital development, and defects in fusion also lead to structural birth defects in these contexts. Despite its importance during development, the mechanical and cell-generated forces that drive tissue fusion are not understood. Our preliminary studies using novel live imaging methodologies reveal dynamic cell behaviors underlying lip and palate fusion and lead us to appreciate the role of cellular mechanical forces and molecular sensors of force required for this process. We will utilize mouse genetics, physical manipulation, and confocal live imaging to define the cell-generated forces, mechanical signaling and dynamic cell behaviors driving lip and palate fusion. These studies take a new approach to understanding tissue fusion during development and will shed light on longstanding questions in the field, leading to improved understanding of structural birth defects that involve tissue fusion.

Public Health Relevance

Cleft lip and palate are common and devastating birth defects that can arise from a failure of tissue fusion during development, a process involving the integration of two separate embryonic primordia into a single continuous structure. Nevertheless, our understanding of tissue fusion is incomplete with a particular gap in knowledge of the mechanical forces and cellular dynamics that drive this event. We propose to test a new model for tissue fusion wherein cell-generated forces drive multiple cell behaviors to facilitate fusion of the upper lip and secondary palate.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE025877-02
Application #
9233992
Study Section
Skeletal Biology Development and Disease Study Section (SBDD)
Program Officer
Scholnick, Steven
Project Start
2016-04-01
Project End
2021-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Dentistry/Oral Hygn
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Kim, Seungil; Prochazka, Jan; Bush, Jeffrey O (2017) Live Imaging of Mouse Secondary Palate Fusion. J Vis Exp :