Gli3 is required for Emx gene expression during dorsal telencephalon development

Dentate gyrus and hippocampus as centers for spatial learning, memory and e motional behaviour have been the focus of much interest in recent years. Th e molecular information on its development, however, has been relatively po or. To date, only Emx genes were known to be required for dorsal telencepha lon development. Here, we report on forebrain development in the extra toes (Xt(J)) mouse mutant which carries a null mutation of the Gli3 gene. This defect leads to a failure to establish the dorsal di-telencephalic junction and finally results in a severe size reduction of the neocortex. In additi on, Xt(J)/Xt(J) mice show absence of the hippocampus (Ammon's horn plus den tate gyrus) and the choroid plexus in the lateral ventricle, The medial wal l of the telencephalon, which gives rise to these structures, fails to inva ginate during embryonic development. On a molecular level, disruption of dorsal telencephalon development in Xt( J)/Xt(J) embryos correlates with a loss of Emx1 and Emx2 expression. Furthe rmore, the expression of Fgf8 and Bmp4 in the dorsal midline of the telence phalon is altered. However, expression of Shh, which is negatively regulate d by Gli3 in the spinal cord, is not affected in the Xt(J)/Xt(J) forebrain, This study therefore implicates Gli3 as a key regulator for the developmen t of the dorsal telencephalon and implies Gli3 to be upstream of Emx genes in a genetic cascade controlling dorsal telencephalic development.