Genetic and Molecular Regulation of Striatal Neurogenesis

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of California
Investigators Name
Yun, Kyuson, PhD

Tourette Syndrome (TS) was originally described by Georges Gilles de la Tourette as a neuropsychiatric disorder characterized by chronic motor and vocal tics that begin in childhood. Since then, family studies have shown that it is inherited as a single autosomal dominant gene with variable penetrance. The discor-dance for symptom severity between identical twins has suggested that prenatal influences and other genetic interactions might modify the clinical expression of this disorder. Therefore, understanding the molecular and genetic regulation of early brain development will be essential to understanding the cause and designing potential treatment strategies for TS. The goal of this project is to utilize the existing mouse mutants that show severe defects in brain development to understand the genetic hierarchy that governs the development of the basal ganglia. The basal ganglia has been implicated in the pathogenesis of Tourette Syndrome and in the mouse mutants that I am studying, Dlx-1/2 null animals, the basal ganglia fails to mature fully. From my recent studies, I hypothesize that Dlx genes lie high up in the hierarchy of regulatory molecules that control the expression of other important genes, and that when Dlx-1/2 are mutated, these downstream genes fail to be expressed properly. I have constructed a working model of genetic interactions among these important regulators, some of which show severe defects in basal ganglia development when mutated themselves. Currently, I am testing this model through molecular and genetic studies. In the process of laying down the foundation of genetic interactions that govern early brain development, we may identify genes that are responsible for, or contribute to several neuropsychiatric disorders, such as TS. At the least, this work will provide a framework of genetic interactions onto which other genes directly related to neuropsychiatric disorders can be superimposed. Kyuson Yun, Ph.D. University of California San Francisco, CA Award: $25,000 Tourette Association of America Inc.- Research Grant Award 1998