Craniofrontonasal syndrome (CFNS) is an X-linked disease that affects multiple aspects of craniofacial development and is caused by mutations in the EFNB1 gene. Frontonasal dysplasia is a defining attribute of CFNS, but the developmental etiology underlying ephrin-B1 function in this context is incompletely defined. We propose to utilize the mouse as a model to understand the basic developmental mechanisms by which EFNB1 acts to control development of the midface. CFNS is an unusual disease in that whereas EFNB1 is an X-linked gene, heterozygous females are more severely affected than hemizygous males. This is related to the fact that heterozygous females represent a mosaic of ephrin-B1 expressing and non-expressing cells. Using a combination of mouse genetics and molecular biology approaches, we will define the mechanistic basis for this phenomenon. Finally, we propose a possible general strategy for preventing CFNS, whose feasibility we will begin to test in a mouse model.

Public Health Relevance

Craniofrontonasal syndrome (CFNS) is an X-linked disease that affects multiple aspects of craniofacial development and is caused by mutations in the EFNB1 gene. This proposal seeks to define the developmental mechanisms underlying CFNS and begin to examine a strategy for therapeutic intervention. This work should provide insight into the developmental functions of EFNB1, and directions for designing preventative or therapeutic strategies for a human birth defect.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE023337-01A1
Application #
8595894
Study Section
Skeletal Biology Development and Disease Study Section (SBDD)
Program Officer
Scholnick, Steven
Project Start
2013-07-09
Project End
2018-05-31
Budget Start
2013-07-09
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$392,500
Indirect Cost
$142,500
Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Dentistry
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143