Fig. 1. In vitro recapitulation of the striatal sorting. (A) Schematic model of development of matrix and striosome compartments in the mouse striatum. Striosomal neurons (in red) are generated first and migrate from the lateral ganglionic eminence (LGE) to the striatal mantle, followed by matrix neurons (in blue). The two populations transiently mix within the striatal mantle, then segregate from each other to form a mosaic of matrix/striosome compartments. (B) A novel organotypic assay to recapitulate the sorting of matrix versus striosome neurons. GFP+ cells are dissociated from the LGE at distinct embryonic ages (E12/E15), and plated onto postnatal striatal slices. The relative distribution of the GFP+ cells is assessed by an M/S value that represents the ratio of the densities of cells that settled in the DARPP32-negative matrix (M) and DARPP32-positive striosome (S) compartments. (C-H) Overlay with E15-LGE derived cells. GFP+ cells preferentially settled in the DARP32-negative matrix compartment (arrows in F-H), while avoiding the DARPP32-positive striosomes (arrowheads). (I-N) Overlay with E12-LGE derived cells. GFP+ cells preferentially settled in the DARP32-positive striosome compartments (arrowheads). (O,P) Quantification of the relative distribution of the GFP+ cells between the striatal compartments. (O) Schematics of the quantification of matrix/striosome cell sorting. The number of GFP+ pixels counted in each striosome (S) and within corresponding areas in adjacent matrix compartment (M) enable to determine a M/S ratio, reflecting the relative distribution of the GFP+ cells in each compartment. (P) E15-LGE and E12-LGE derived cells display very different M/S values (^*P<0.0001), respectively greater than and less than 1, reflecting their preference for complementary compartments, contrary to a control thalamic cell population. Scale bar: 200 µm.