| Popis: |
The embryonic telencephalon gives rise to a complex organization of neuronal nuclei that control cognition and voluntary movement. The lateral ganglionic eminence (LGE), a sub-region of the ventral telencephalon, is a known source of two distinct cell populations, striatal projection neurons and olfactory bulb interneurons. The current studies were aimed at elucidating the molecular pathways involved in the generation of these neuronal cell types. The homeobox gene, Gsh2 is required for the generation of striatal projection neurons and olfactory bulb interneurons. Initially, characterization experiments were undertaken to dissect additional roles for Gsh2 in the developing LGE. The requirement of Gsh2 for retinoid production in the LGE indicates for the first time that Gsh2 may have a role independent of repressing dorsal telencephalic gene expression in the ventral telencephalon. Moreover, the reduced retinoids in the Gsh2 mutant were shown to contribute to the striatal differentiation defects. Gsh2 mutants also exhibit defects in the generation of olfactory bulb interneurons. It has recently been suggested that these cells derive from a distinct progenitor domain in the dorsal LGE (dLGE), which requires Gsh2 for its normal formation (Stenman et al., 2003a). A novel requirement of Gsh2 shown here for the expression of the zinc-finger transcription factor Sp8 in the dLGE provides further support for this notion. In addition, further analysis of embryonic and postnatal Sp8 expression and the loss of Sp8 in the dLGE (Sp8 conditional mutant) suggests the existence of neuronal diversity in the dLGE, in the postnatal progenitor regions for olfactory bulb interneurons (the rostral migratory stream and the subventricular zone), and in differentiated olfactory bulb interneurons. Taken together these studies describe novel requirements for Gsh2 during LGE development and identify a novel genetic pathway that contributes to neuronal diversity of olfactory bulb interneurons. Finally, the generation of a conditional mutant allele of Gsh2 and strategy for a telencephalon specific mutant provides for the first time a genetic tool to address both spatial and temporal (e.g. postnatal) roles for this gene. |
