Research in E.Y.I.’s laboratory is supported by the NIH (R01NS035549) and NSF (FIBR 0623527). This work was funded by a European Research Council Starting Independent Researcher Grant to R.B. “
“Cortical GABAergic interneurons are generated in multiple progenitor zones of the subpallial (subcortical)

telencephalon, including the lateral, medial, and caudal ganglionic eminences (LGE, MGE, and CGE) (Anderson NLG919 et al., 1997a, Anderson et al., 2001, Butt et al., 2005, Fogarty et al., 2007, Marin and Rubenstein, 2003, Pleasure et al., 2000, Sussel et al., 1999 and Wonders and Anderson, 2006). The specification, differentiation, and migration of these cells are regulated by multiple transcription factors, including the Dlx1,2,5,6 and Lhx6 homeobox genes. The Dlx genes are critical for interneuron migration and differentiation. For example, mice lacking Dlx1/2 show a block in the migration of most cortical and hippocampal interneurons ( Anderson et al., 1997a and Pleasure et al.,

2000). Mice lacking Dlx1 show defects in dendrite-innervating interneurons ( Cobos et al., 2005), whereas mice lacking either Dlx5 or Dlx5/6 have defects in somal-innervating (parvalbumin+; PV+) interneurons ( Wang et al., 2010). Studies on transcriptional alterations in the Dlx1/2–/– mutants have begun to elucidate the molecular pathways that regulate interneuron development and

function ( Long et al., 2009a and Long et al., 2009b). We have discovered that the Dlx genes promote the expression of two chemokine receptors, CXCR4 and CXCR7 (RDC1; CMKOR1) ( Long et al., Y-27632 clinical trial 2009a, Long et al., 2009b and Wang et al., 2010). Furthermore, these receptors are also positively regulated by the Lhx6 transcription factor ( Zhao et al., 2008) that is essential for the differentiation of PV+ and somatostatin+ (SS+) interneurons Megestrol Acetate ( Liodis et al., 2007 and Zhao et al., 2008). CXCR4 and CXCR7 are seven-transmembrane receptors that bind CXCL12, a chemokine also known as Stromal-derived factor 1 (SDF1) (Balabanian et al., 2005 and Libert et al., 1991). CXCL12 binding to CXCR4 triggers Gαi protein-dependent signaling, whereas CXCl12 binding to CXCR7 does not activate Gαi signaling (Levoye et al., 2009 and Sierro et al., 2007). On the other hand, many lines of evidence indicate that CXCR7 has an important role in regulating cell signaling in culture and in vivo. In developing zebrafish, CXCR4 and CXCR7 are both implicated in regulating migration of primordial germ cells (PMGs) and the posterior lateral line primordium, in part through their differential expression patterns (Boldajipour et al., 2008, Dambly-Chaudiere et al., 2007 and Valentin et al., 2007). For instance, while CXCR4 is expressed in the germ cells, CXCR7 is expressed in adjacent cells.