Because PCDH17 was mostly expressed along the medial prefrontal cortex-anterior striatal pathways in a topographic manner, in both rodents and primates, it is likely that PCDH17 is anatomically and functionally conserved in the corticobasal

ganglia circuits of higher primates as well. Therefore, the PCDH17-expressing neuronal pathway could correspond to the prefrontal cortical loops in primates used for processing CB-839 chemical structure some aspects of motivational and executive functions. As the complementary expression patterns of PCDH17 and PCDH10 appear at E14.5 and gradually develop in the embryonic mouse striatum until birth (our unpublished data), we assumed that the expression of these protocadherins was reciprocally regulated by positional information in the embryonic striatum. Nevertheless, PCDH17 is dispensable R428 research buy in this topographic map formation (Figure S4), although it has crucial roles in the synaptic development of this pathway. In addition to these protocadherins, some axon guidance molecules that are involved in topographic map

formation in the visual and olfactory systems (Luo and Flanagan, 2007; Sakano, 2010), are also expressed in the embryonic striatum in a zone-specific manner. Like PCDH17, Netrin-1 exhibits an expression pattern with a high-anterior to low-posterior gradient in embryonic striatal regions (Powell et al., 2008). In contrast, similar to PCDH10, Ephrin-A5 and Semaphorin-3A exhibit expression patterns with low-anterior to high-posterior gradients

(Dufour et al., 2003; Wright et al., 2007). Therefore, these axon guidance molecules might organize the topographic map delineated by PCDH17 and PCDH10 expression in the embryonic basal ganglia. PCDH10−/− mice exhibit axonal growth defects in the striatum and die within the first several weeks after birth ( Uemura et al., ADP ribosylation factor 2007), whereas PCDH17−/− mice do not die prematurely and are not characterized by abnormal striatal axonal growth. These phenotypic differences may be at least partially attributable to different protein distributions in embryonic striatal fibers; PCDH10 ( Uemura et al., 2007), but not PCDH17 (our unpublished data), is distributed around striatal fibers at E14.5. It should be noted that similar to that of PCDH17, the expression of PCDH10 peaks during early synaptogenesis. A recent paper showed that PCDH10 is required for activity-dependent synapse elimination in cultured neurons ( Tsai et al., 2012). Therefore, PCDH10 may function not only in axonal growth, but also in synaptic development of corticobasal ganglia circuits.