Potential target genes of EMX2 include Odz/Ten-M and other gene families with implications for cortical patterning

EMX2 and PAX6 are expressed by cortical progenitors and specify area patterning. We used representational difference analysis (RDA) to compare expressed RNAs from wild type and Emx2−/− cortex and identified 41 unique clones. Using secondary screening by in situ hybridization, we selected five genes for further analysis, Cdk4, Cofilin1, Crmp1, ME2, and Odz4, involved in neuronal proliferation, differentiation, migration, and axon guidance. Each exhibits differential expression in wild type cortex. Odz4 is one of four members of a vertebrate gene family homologous to the Drosophila pair-rule patterning gene, Odd Oz (Odz), a transmembrane receptor. We show that Odz genes are expressed in complementary patterns in cortex, as well as in nuclei-specific patterns in thalamus that relates to their area-unique cortical expression. In addition, each of the genes analyzed shows different expression patterns in wild type cortex, Emx2, and Pax6 mutant cortex, consistent with potential roles in area patterning. These findings identify potential targets of EMX2 that might account for its function and the defects in Emx2−/− cortex, and suggest that the Odz family of transmembrane proteins influences cortical area patterning downstream to EMX2 and PAX6.