Next, we compared the laminar distribution of Lhx6+ cells in both mutants and we found that they had very similar defects: reduced numbers of Lhx6+ cells in Screening Library clinical trial the MZ and SVZ, and an increase in the number of Lhx6+ cells in the CP, especially in the lower CP ( Figures 3A″–3C″ and 3E). Thus, both Cxcr7 and Cxcr4 had similar functions in maintaining interneurons within

the MZ and SVZ migratory streams and in controlling the timing for interneuron invasion into the cortical plate. While Cxcr4−/− and Cxcr7−/− mutants share very similar interneuron laminar positioning phenotypes in the cortical plate, these deficits may arise from distinct alterations in migration dynamics. To further explore the migration behaviors of Cxcr4−/− and Cxcr7−/− interneurons in vivo, we performed real-time imaging of Lhx6-GFP+ cortices from control (Cxcr4+/− or Cxcr7+/−), Cxcr4−/−, and Cxcr7−/− embryos at E15.5. We first examined the transition from tangential to radial migration as interneurons migrated from either the MZ or the SVZ into the CP. In the MZ, Cxcr4−/− and Cxcr7−/− mutants demonstrated a 3-fold and 2.4-fold increase in the number of Lhx6-GFP+ interneurons C646 chemical structure switching from tangential to radial migration, respectively ( Figures 4A–4C and 4G; Movies S1–S3). In the SVZ, Cxcr4−/− mutants displayed a 2-fold increase in the number of Lhx6-GFP+

interneurons switching from tangential to radial migration and no effect was detected in the Cxcr7−/− mutants ( Figures 4D–4F and 4H; Movies S4–S6). Therefore, the laminar deficits from both mutants were mainly due to an increased number of Lhx6-GFP+ cells moving from either the MZ or the SVZ into the cortical plate. Next, we studied the tangential

migration rate of Lhx6-GFP+ cells that were maintained in the MZ and SVZ during the 20-hour live-imaging session. Compared to controls, Cxcr7−/− mutants exhibited a substantial decrease in tangential migration rate in the MZ and SVZ; and Cxcr4−/− mutants displayed a modest decrease in migration rate in the SVZ ( Figure 4I). Thus, Methisazone the decreased migration rate may underlie the reduced extent of interneuron migration into the dorsal cortex observed in both mutants during early embryonic stages. Finally, we explored the migration behaviors of Lhx6-GFP+ cells after they entered into the cortical plate. Cxcr4−/− and Cxcr7−/− mutants displayed major differences in interneuron motility and leading process morphology. Cxcr4−/− mutants exhibited a significant increase in the number of motile cells and in the leading process length of tangentially oriented cells, while Cxcr7−/− mutants showed a significant decrease in the number of motile cells and in the leading process length of both radially and tangentially oriented cells ( Figure 5 and Movies S7–S9).