The striatum, the largest basal ganglia controlling motor functions of the brain, can be characterized by the mosaic organization of striosome and matrix compartments. Striosome forms a labyrinthine-like patchy structure, whereas the matrix surrounds the clusters of striosome. Imbalances in the function of striosome/matrix compartments were suggested to be involved in many basal ganglia disorders. It is therefore crucial to understand how striosome/matrix mosaic compartment is established during the striatal development.
To understand spatial and temporal regulation of striosome/matrix mosaic formation, here we differentially labeled striosome and matrix cells from their time of birth and followed their distributions and migratory behaviors prospectively by combining in vivo electroporation-mediated gene transfer and brain slice cultures. Our analyses revealed that striosome cells were mostly stationary whereas matrix cells were actively migrating in multi-directions at early embryonic stages. Patchy clusters of striosome cells appeared to be formed initially through their mutual homophilic interactions per se, mediated by their intertwined extended processes. Only at late-embryonic stages, repulsive migratory behaviors between striosome and matrix cells were observed. These results suggested that restricted migratory capability of striosome cells may only allow them to cluster together when they were closely juxtaposed with each other. Actively migrating matrix cells occupied the space in between the striosome cells and may interfere with striosome clustering. The way actively migrating matrix cells intermingle with mostly stationary striosome cells may therefore determine the size, number and possibly the position of patchy clusters of striosome cells within the striatum. The repulsive migratory behaviors of matrix cells at later developmental stages against striosome patchy clusters presumably contribute to the segregation and formation of dichotomous homogeneous striosome/matrix compartments. Taken altogether, our study revealed distinct migratory behaviors of striosome and matrix cells, which may underlie the sequential cascades of striosome/matrix mosaic formation in the developing striatum.