The Gsh2 homeodomain gene controls multiple aspects of telencephalic development

Homeobox genes have recently been demonstrated to be important for the prop er patterning of the mammalian telencephalon, One of these genes is Gsh2, w hose expression in the forebrain is restricted to the ventral domain. In th is study, we demonstrate that Gsh2 is a downstream target of sonic hedgehog and that lack of Gsh2 results in profound defects in telencephalic develop ment, Gsh2 mutants have a significant decrease in the expression of numerou s genes that mark early development of the lateral ganglionic eminence, the striatal anlage, Accompanying this early loss of patterning genes is an in itial expansion of dorsal telencephalic markers across the cortical-striata l boundary into the lateral ganglionic eminence. Interestingly, as developm ent proceeds, there is compensation for this early loss of markers that is coincident with a molecular reestablishment of the cortical-striatal bounda ry. Despite this compensation, there is a defect in the development of dist inct subpopulations of striatal neurons. Moreover, while our analysis sugge sts that the migration of the ventrally derived interneurons to the develop ing cerebral cortex is not significantly affected in Gsh2 mutants, there is a distinct delay in the appearance of GABAergic interneurons in the olfact ory bulb, Taken together, our data support a model in which Gsh2, in respon se to sonic hedgehog signaling, plays a crucial role in multiple aspects of telencephalic development.