As the face develops, stem cells have the potential to become cartilage, bones, or teeth. Researchers at the University of Southern California Stem Cell Crump Lab recently explored whether a key family of genes known as Forkhead-domain transcription factors, or Fox for short, play a role in this development. Mutations in Fox genes, for example, can cause diseases ranging from cancer to language disorders.
“While examination of Fox genes in the mammalian face reveals they are required for bone and palate formation, whether Fox genes broadly control regional facial skeletal fates, as well as their mechanisms of action, remains unclear,” said postdoc Pengfei Xu, PhD.
The researchers created mutant zebrafish that lacked Fox-C or Fox-F genes. The fish lacking Fox-C failed to form cartilage in their upper face. The fish lacking Fox-F genes had problems developing their jaws, cartilage in the middle of their faces, and teeth. Further experiments revealed that Fox-C and Fox-F help another important gene, Sox9, activate additional genes that promote cartilage development in the embryo.
Other laboratories have noted similar effects in mice lacking Fox genes. These findings suggest that the Fox genes play a role in the facial development of not only zebrafish and mice, but also many other vertebrate species, including humans.
“Transcription factors like Sox9 play roles in many different organs in the body,” said Gage Crump, PhD, professor of stem cell biology and regenerative medicine. “This tour-de-force genetic study shows how a family of Fox factors direct cells to form only cartilage and teeth and not other cell types. This may help in strategies toward directing stem cells to form cartilage and teeth for future regenerative medicine applications.”
The study, “Fox Proteins Are Modular Competency Factors for Facial Cartilage and Tooth Specification,” was published by Development.
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