MUTATIONS OF THE HOMEOBOX GENES DLX-1 AND DLX-2 DISRUPT THE STRIATAL SUBVENTRICULAR ZONE AND DIFFERENTIATION OF LATE BORN STRIATAL NEURONS

The striatum has a central role in many neurobiological processes, yet little is known about the molecular control of its development. Inroa ds to this subject have been made, due to the discovery of transcripti on factors, such as the Dlx genes, whose expression patterns suggest t hat they have a role in striatal development. We report that mice lack ing both Dlx-1 and Dlx-2 have a time-dependent block in striatal diffe rentiation. In these mutants, early born neurons migrate into a striat um-like region, which is enriched for markers of the striosome (patch) compartment. However, later born neurons accumulate within the prolif erative zone. Several lines of evidence suggest that mutations in Dlx- 1 and Dlx-2 produce abnormalities in the development of the striatal s ubventricular zone and in the differentiation of striatal matrix neuro ns.