Mutations in the Eml1 gene are responsible for severe cortical malformation in humans, reports a study published online this week in Nature Neuroscience. These findings expand our knowledge of the genes and mechanisms involved in congenital brain disorders.

Subcortical band heterotopia (SBH) is a form of cortical malformation associated with intellectual disability and epilepsy in humans. It is thought to be the result of defects in neuronal migration, the brain-building process by which immature cortical neurons travel from their fetal location to their final destination in the adult brain.

Fiona Francis and colleagues used a mouse model of subcortical heterotopia to study the causes of cortical malformations. The researchers found that heterotopia in these mice was due to a mutation in Eml1, a gene encoding a protein associated with the cellular structures involved in cell shape and division. They also found that mutations in Eml1 disrupted the function of specialized cells called neural progenitors, which are responsible for the production of cortical neurons during the prenatal period.

In this heterotopia mouse model, neural progenitors detached from their usual location near the ventricles and migrated toward the cortex where they produced neurons but in an inappropriate location. This resulted in the heterotopia observed in the mice. The authors then screened patients with cortical malformations for potential mutations in Eml1; in agreement with the animal results, they found mutations in the Eml1 gene in two unrelated families of patients suffering from severe heterotopia.