Cerebellum Circuit Formation in Engrailed Mutant Mice
Memorial Sloan-Kettering Cancer Center
It has long been known that people with autism have abnormalities in the cerebellum, a brain structure that controls movements and processes sensory information. Neuropathological studies have reported a loss of cells in the cerebellum, called “hypoplasia”; however, it is unknown what causes this cellular defect. Dr. Joyner and her team have focused in part on a gene called ENGRAILED2 (En2), which other studies have linked to autism, hypothesizing that mutations of this gene lead to a loss of cells in specific areas of the cerebellum. This hypoplasia may produce failure to execute particular motor and sensory brain operations that would normally emerge during early development and are typical of autism spectrum disorders. Using state-of-the-art molecular biology techniques, Drs. Joyner and Sillitoe will examine how neuronal circuits in the cerebellum are affected by loss of the En2 gene. They will focus on one particular cell type, the Purkinje cells, which form the primary pathway in which the cerebellum connects with other parts of the brain. What this means for people with autism: This research will advance a promising line of research into abnormalities in the cerebellum and their role in autism. In particular, it will investigate how the En2 and En1 genes affect cell growth and neural circuitry in the cerebellum. This work will provide insight into specific cerebellum-associated deficits in autistic children and thus could lead to behavior modification protocols aimed at improving their prognosis.