The LIM homeobox gene Isl1 is required for the correct development of the striatonigral pathway in the mouse

The basal ganglia process cortical information that controls purposeful movements and appropriate behavior via the striatopallidal and striatonigral pathways. Despite their importance, little is known about the developmental mechanisms that control the formation of these pathways. We show here that telencephalic progenitors expressing the transcription factor Islet1 give rise to striatonigral neurons and that this factor is required for normal development of the striatonigral pathway. Moreover, Islet1 mouse mutants exhibit hyperactivity and a paradoxical response to psychostimulants. Given that the underlying causes of basal ganglia disorders such as attention deficit hyperactivity disorder (ADHD) are unknown, these findings may implicate possible alterations in neural circuitry.