Lab Identifies Cellular Cause of Treacher Collins Syndrome

The lab team of Paul Trainor, Ph.D., Assistant Investigator, has collaborated with colleagues from the University of Manchester Dental School in the U.K. on a paper that identifies the cellular origins for craniofacial abnormalities that occur in Treacher Collins syndrome. Natalie Jones, Ph.D., Postdoctoral Research Associate, and Dr. Trainor are credited as the first and last authors, respectively.

Treacher Collins syndrome is a rare disorder of craniofacial development affecting about 1 in 50,000 individuals. It is characterised by ear, nose, upper, and lower jaw anomalies that include cleft palate. The findings, published in the September 5 issue of the Proceedings of the National Academy of Sciences (PNAS), establish that the craniofacial anomalies associated with a mouse model of Treacher Collins syndrome arise due to a high degree of cell death, which leads to a failure to produce sufficient neural crest cells. Moreover, the team found that the few neural crest cells that are produced have compromised proliferation capacities. “Since neural crest cells ultimately form most of the bone, cartilage, and connective tissue in the head and the face, it is not surprising that a deficiency in the number of neural crest cells leads to craniofacial malformations,” said Dr. Jones. The team believes that when translated to human development, these findings indicate that within the first 3-8 weeks of pregnancy, a similar period of extensive cell death results in a failure to produce enough neural crest cells and causes the facial characteristics observed in individuals with Treacher Collins syndrome. “These findings are an exciting step in our investigation of genetic birth abnormalities,” said Dr. Trainor. “In ongoing studies in the lab, we are testing a number of methods for chemically and genetically inhibiting the early period of cell death, known as apoptosis, in an effort to stimulate the production of neural crest cells which could help to prevent the development of craniofacial anomalies.” “These results represent a major breakthrough in our understanding of Treacher Collins syndrome,” said Robb Krumlauf, Ph.D., Scientific Director. “But the door that these findings open-to the possibility of intervening in utero to prevent the disease-is truly groundbreaking.”(Source: Proceedings of the National Academy of Sciences: Stowers Institute: September 2006).