UCLA Dental School study sheds new light on genetic facial disorder

Posted on: Friday, 07/31/2009


A study by researchers at the UCLA School of Dentistry provides new insight into the underlying causes of a rare genetic disorder known as oculo-facial-cardio-dental syndrome (OFCD). The disease, which is characterized by canine teeth with extremely long roots, congenital cataracts, craniofacial defects and congenital heart disease, is associated with mutations in BCOR, a protein that shuts down gene expression during fetal development.

Dr. Cun-Yu Wang, who holds UCLA's No-Hee Park Endowed Chair in Dentistry, and colleagues show that mesenchymal stem cells isolated from the roots of the teeth of OFCD patients have an enhanced tendency to develop into dental and bone cells, that expressing BCOR in these cells can reverse this process, and that removing BCOR from healthy cells results in the increased formation of bone and dental cells. The researchers also show that removing AP-2 alpha, a genetic transcription factor also involved in craniofacial development, from mesenchymal stem cells reverses their development into cells that form bone and teeth.


The findings, which provide a molecular explanation for the exaggerated dental and craniofacial features seen in patients with OFCD, unravel the epigenetic mechanisms that control human adult stem-cell function. This may lead to a treatment for OFCD, as well as to new therapies for promoting the growth of teeth and bone.


Zhipeng Fan, Jinhua Yu and Cun-Yu Wang of the UCLA School of Dentistry; Guoping Fan of the David Geffen School of Medicine at UCLA; Takayoshi Yamaza and Songtao Shi of the University of Southern California; Janice S. Lee of the University of San Francisco; and Songlin Wang of the Capital Medical University School of Stomatology in Beijing, China.

The research was supported by grants from the National Institute of Dental and Craniofacial Research and by the Shapiro Family Charitable Foundation.


The research appears online and in print in the August issue of the peer-reviewed journal Nature Cell Biology.


The full paper and corresponding imagery can be viewed online.