We first performed microtransplantation assays in slices, as described before ( López-Bendito et al., 2008) ( Figure 8A). We previously showed that E13.5

wild-type MGE-derived interneurons isochronically transplanted into the cortex disperse tangentially and avoid entering the CP, as they normally do in vivo, whereas Cxcr4 mutant interneurons prematurely invade the CP ( López-Bendito et al., 2008). Unexpectedly, the migration of Cxcr7 mutant interneurons transplanted into wild-type cortices was indistinguishable from that of wild-type Adriamycin cells ( Figures 8B, 8D, and 8E). Furthermore, we observed that most Cxcr7 mutant interneurons contained detectable levels of Cxcr4 while migrating into wild-type slices ( Figures 8C and 8F), which demonstrated that the function of Cxcr7 in nearby interneurons is enough

to sustain the levels of Cxcr4 receptors in Cxcr7 mutant interneurons. To confirm these selleck compound library observations, we next carried out similar transplantation experiments in vivo (Figure 8G). We previously showed that E15.5 wild-type interneurons transplanted isochronically and homotypically in utero end up primarily in superficial layers of the cortex (López-Bendito et al., 2008 and Pla et al., 2006), as they normally do in vivo. In contrast, many E15.5 Cxcr4 mutant interneurons end up in deep cortical layers, probably because they prematurely invade the CP ( López-Bendito et al., 2008). As predicted by our organotypic cultures, E15.5 MGE-derived Cxcr7 mutant interneurons transplanted into wild-type embryos adopt a laminar pattern that is indistinguishable

from control interneurons born isochronically ( Figures 8H and 8I). Altogether, our experiments demonstrated that Cxcr7 is not essential within each individual interneuron for their migration. Instead, these results revealed that Cxcr7 functions at the population level to regulate the migration of cortical interneurons. In this study, we have used cortical interneurons as a model system to investigate the function of the mafosfamide atypical chemokine receptor Cxcr7 in neuronal migration. We have found that Cxcr7 is required in migrating interneurons to regulate the levels of Cxcr4 receptors expressed by these cells, through a process that requires the interaction of migrating cells with the chemokine Cxcl12. Interestingly, this function emerges as a property of the entire population of migrating interneurons, because the loss of Cxcr7 in an individual cell can be rescued by the function of Cxcr7 in other migrating interneurons. These results provide a clear demonstration that an atypical chemokine receptor can modulate the highly specialized function of a classical chemokine receptor by controlling the amount of receptor that is made available for signaling at the cell surface.