Skip to main content

Clues to flattened faces

Jan. 5, 2012, 4:22 PM

Images of individuals with Alagille syndrome (National Institutes of Health)
Images of individuals with Alagille syndrome (National Institutes of Health)

Mutations in the Jagged1 gene cause Alagille syndrome, an inherited disorder that affects the liver, heart, kidneys and facial structure. Patients with Alagille syndrome often have a prominent forehead, a flattened midface and a prominent chin; some have a cleft palate.

To investigate how mutations in Jagged1 cause facial anomalies, Steven Goudy, M.D., and colleagues deleted the Jagged1 gene in mouse cranial neural crest cells – the main cell type that contributes to craniofacial development. They found that these mice had midfacial hypoplasia (incomplete development) similar to patients with Alagille syndrome. The studies point to a requirement for Jagged1 signaling at a specific time during midface and palate formation, for proper cellular division and extracellular matrix production. The researchers also found reduced branching of blood vessels, which could explain why some patients with Alagille syndrome are at risk of cerebral vascular bleeding.

The findings, reported in Human Molecular Genetics, suggest that Jagged1 acts on cranial neural crest cells both directly and indirectly to form the middle of the face.

This research was supported by the National Institute of Dental and Craniofacial Research, the National Heart, Lung and Blood Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases.

Recent Stories from VUMC News and Communications Publications

Keeping pace: Nashville, once a mid-size city with a Southern small-town feel, is experiencing explosive growth.

Vanderbilt Medicine

Keeping pace: Nashville, once a mid-size city with a Southern small-town feel, is experiencing explosive growth.

VUMC campus

VUMC campus

Vanderbilt University School of Medicine entrance

Vanderbilt University School of Medicine entrance

Vanderbilt University Adult Hospital with helipad

Vanderbilt University Adult Hospital with helipad

more