Fig. 9. Schematic of homeodomain interactions that pattern the telencephalon. Diagram represents a coronal hemisection of an E12.5 telencephalon showing domains of homeodomain gene expression. The outline of the major genetic interactions governing telencephalic development is incorporated from the results of this study and others (Wilson and Rubenstein, 2000; Schuurmans and Guillemot, 2002; Rallu et al., 2002b; Campbell, 2003). Shh, via repression of the repressive action of Gli3, is required for normal ventral patterning. Shh is necessary and sufficient for the expression of Nkx2.1, which functions to repress LGE character in the MGE. However, this function of Nkx2.1 is not mediated through repression of Gsh1 and/or Gsh2. Conversely, Gsh1 and Gsh2 are not required to repress Nkx2.1 expression. By contrast, Gsh2, whose expression is regulated both via Shh-dependent and Shh-independent pathways, functions to repress dorsal character in all but the ventral-most one third of the LGE via cross-repression with Pax6. Patterning of the ventral-most one third of the LGE is dependent on Gsh1 gene function, whose expression, similar to Nkx2.1, is dependent on Shh. Expression of Dlx2, Mash1 and Olig2 is mediated either directly through Gsh1 and Gsh2 and/or indirectly through Pax6. Residual expression of Dlx2, Mash1, Olig2 and Gad67 in Nkx2.1^–/–;Gsh2^–/– mutants is hypothesized to be attributable to the persistence of Gsh1 expression.

Return to article