Figure 2. Summary of graded expression of transcription factors implicated in arealization and findings in mouse mutants.

(A) Graded expression in cortical progenitors of the transcription factors directly implicated in arealization, Emx2, Pax6, Coup-TFI, and Sp8, along the anterior-posterior (A–P) and lateral-medial (L–M) axes of the cortex. (B) Summary of reports of loss- or gain-of-function mutant mice of TFs that exhibit changes in area patterning. Mice with a targeted deletion of Emx2 die at birth, but late embryonic analyses suggest substantial changes in arealization as indicated in the cartoon, with a reduction in posterior areas and an expansion and posterior shift of anterior areas. Reducing Emx2 levels in the cortex of the heterozygote mutant mice (Emx2 KO het) results in posterior shifts of areas with shrinkage of V1, while overexpression of Emx2 under the control of nestin promoter (Nestin-Emx2 Transgenic) shifts areas anteriorly. Small eye mutant mice, which lack functional Pax6 protein, die at birth, but marker analyses suggest a reduction in anterior areas and an expansion and anterior shift of posterior areas. However, YAC transgenic mice of Pax6 do not show area changes other than a slight, but significant, reduction in the size of S1 (asterisk). Selective deletion of COUP-TFI in conditional knockout mice crossed with an Emx1-Cre line results in a massive expansion of frontal/motor areas and a substantial reduction of the primary sensory areas that shift posteriorly to the posterior cortical margin. Analyses of conditional knockout mice of Sp8 crossed to a BF1 (Foxg1) Cre line shows at late embryonic ages anterior shifts of gene markers, a phenotype similar to that reported for Fgf8 hypomorphic mice. The BF1-Cre line deletes Sp8 not only from cortical progenitors but also from the CoP, resulting in diminished expression of Fgf8 in the CoP. See text for details and references.