First genetic model of a human jaw fusion defect known as SYNGNATHIA

Almost a third of all birth defects involve the head and face and most can be blamed on problems relevant to neural crest cells. These cells spring from neural tissue of the brain and embryonic spinal cord and travel throughout the body, where they morph into highly specialized bone structures, cartilage, connective tissue, and nerve cells. Occasionally, neural crest cell development goes awry, causing birth defects affecting regions as diverse as the head, heart or gut. (See cover story for more on neural crest cells.)

In a recent study, Paul Trainor, PhD, and his team characterized a mutant mouse that mimics a congenital disorder known as syngnathia in which children are born with fused upper and lower
jaws and related facial anomalies. They discovered that neural crest cells predestined to build the afflicted facial areas are formed normally and migrate properly, but mature incorrectly.

The Trainor lab also focuses on congenital malformations caused by impaired neural crest cell expansion or migration, such as the rare disorder Treacher Collins syndrome, in which children exhibit small cheekbones and jaws together with cleft palate, drooping eye slits and ear anomalies leading to hearing loss.

“In a condition like Treacher Collins we see a failure to make enough cells at the beginning of migration due to mutations in Tcof1, while in syngnathia cells form properly but make bone in an inappropriate place due to loss of Fpxc1,” says Trainor. “This means there simply isn’t going to be any one uniform way to address all of these disorders. If you want to prevent or treat them you must understand how each originates cellularly and genetically.”

The study was published in the December 19, 2013, issue of PLOS Genetics.