Role of Sp8 in the forebrain. (a) A scheme illustrating the genetic interplay between Sp8 and Emx2. Emx2 and Pax6 mutually affect their graded expression characteristics along the A/P axis (red and blue arrows). Sp8 acts as a repressor of Emx2 to pattern the forebrain along the A/P axis. In cKO, the mutant Emx2 expression domain (red) is expanded rostrally. Accordingly, Pax6 expression territory (blue) is diminished. (b) Scheme recapitulating the gene expression of marker genes at the medial and lateral PSB. In conditional Sp8 mutant, a dorsalization of gene activity around the midline occurs, as highlighted by the ventral expansion of the domain marked in red. Dorsal: red domain, Pax6, Emx2, Ngn2; ventral: green and light-green domain, Gsh2, Dlx1, Mash1. Reciprocally, the expression area of ventral markers is lost in the dorsal septum (light green domain). Accordingly, Fgf8 and Nkx2.1 expression domains are not maintained in the mutant cortical midline. We favor a model in which Sp8 regulates the AP regionalization of cortex by directly suppressing Emx2, while the role of Sp8 in the maintenance of Nkx2.1 activity in SE and MGE could consist of controlling Fgf8.