An animal model may explain how skull malformations (eg, cleft lip/palate and congenitally missing teeth) occur and how they might be prevented. A group led by Yang Chai at the USC School of Dentistry has identified the genetic factor leading to malformation of the forehead and frontal part of the skull. The discovery was published online December 20 by the journal Development.
A gene called TGF-beta plays an important role in human and animal development. Researchers deleted TGF-beta in mice embryos only in the cranial neural crest cells that build facial bone and cartilage. The rest of the embryo’s cells were allowed to retain the gene and grew normally. Mice born from the treated embryos carried severe craniofacial defects, indicating that TGF-beta is necessary for proper development of frontal bones. Further, embryos missing TGF-beta could be rehabilitated by inoculation with FGF, an intermediate protein in the “signaling cascade,” starting with TGF-beta and ending with healthy facial structures. Researchers concluded that TGF-beta acts through FGF to ensure proper development.
Although current results apply only to mice, a paper by Loeys, et al (Nature Genetics, 2005) identified a handful of human families with inherited mutations in TGF-beta receptors and with a high incidence of craniofacial defects. If the signaling mechanism in mice carries over to humans, FGF could be a potential supplement for pregnant women.
(Source: University of Southern California News Service, December 22, 2005)
