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.
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.
