The inverse gradients of the ligand and its receptor in the developing cortex are intriguing, because

CXCR7 has been reported to act as a scavenger receptor that can reduce the concentration of CXCL12 available for signaling ( Boldajipour et al., 2008). Possibly, CXCR7 in the cortical plate may lower the concentration of CXCL12 and generate a gradient from VE-822 in vitro either MZ or SVZ to the cortical plate, thereby regulating the cortical invasion of migrating interneurons. In our study, elimination of Cxcr7 in the cortical plate may disrupt this gradient and thus results in a premature interneuron entry. Several transcription factors have been demonstrated to regulate the migration of interneurons generated from the ganglionic eminences; these

include Arx, Dlx1, Dlx2, Dlx5, Lhx6, Nkx2.1, and Sox6 ( Alifragis et al., 2004, Anderson et al., 1997a, Anderson et al., 1997b, Azim et al., 2009, Batista-Brito et al., 2009, Casarosa et al., 1999, Colasante et al., 2008, Liodis et al., 2007, Marin et al., 2000, Nobrega-Pereira et al., 2008, Pleasure et al., 2000, Sussel et al., 1999 and Zhao et al., 2008). DAPT price Effector downstream genes that are implicated in regulating interneuron migration such as Cxcr4 and Cxcr7 are beginning to be identified ( Long et al., 2007, Long et al., 2009a, Long et al., 2009b and Zhao et al., 2008). In Dlx1/2−/− double mutants, expression of Cxcr4 and Cxcr7 is greatly reduced in cortical interneurons and the ganglionic eminences ( Figure S5;

Long et al., 2009a and Long et al., 2009b). Our data provide evidence that CXCR4 and CXCR7 function is not required for interneurons to migrate from the ganglionic eminences to the cortex ( Figure 3), whereas in Dlx1/2−/− mutants the migration block is nearly complete ( Anderson et al., 1997a and Long et al., 2007). Thus, other factors must contribute to the failure of interneuron migration in the Dlx1/2−/− mutants such as overexpression of Pak3 ( Cobos et al., 2007). On the other hand, Lhx6, Cxcr4, and Cxcr7 mutants share similar defects in interneuron migration rate and loss from the cortical MZ ( Zhao et al., 2008). Lhx6 mutants have greatly reduced Cxcr4 and Cxcr7 expression ( Zhao 3-mercaptopyruvate sulfurtransferase et al., 2008). Thus, it is appealing to conclude that failure to express these receptors is a principle mechanism contributing to the interneuron migration defects in Lhx6 mutants. All experimental procedures were approved by the Committees on Animal Health and Care at the University of California, San Francisco (UCSF). Mouse colonies were maintained at UCSF in accordance with National Institutes of Health and UCSF guidelines. Cxcr4 null mice were previously described ( Ma et al., 1998 and Stumm et al., 2003). The Dlx5/6Cre and DlxI12bCre lines were previously described ( Kohwi et al., 2007 and Potter et al., 2009), and the Lhx6-GFP Cxcr7-GFP BAC lines were purchased from The Gene Expression Nervous System Atlas Project (GENSAT) at The Rockefeller University (New York, NY).