Disease relevance of Gsh2

• We have previously shown that despite the maintenance of important regulatory genes such as Gsh2, in vitro expansion of cells from the lateral ganglion eminence (LGE) restricts their differentiation potential [1].

High impact information on Gsh2

• During the embryonic period, many olfactory bulb (OB) interneurons arise in the lateral ganglionic eminence (LGE) from precursor cells expressing Dlx2, Gsh2 and Er81 transcription factors [2].
• The homeodomain transcription factor Gsh2 is expressed in the progenitors of three dorsal interneuron subtypes, dI3, dI4 and dI5 neurons, whereas Gsh1 is only expressed in dI4 and dI5 progenitors [3].
• Our results provide evidence that genetic interactions involving repression of Ngn1 by Gsh2 promote the differentiation of dI3 neurons from class A progenitors [3].
• Mice lacking Gsh2 exhibit a selective loss of dI3 interneurons that is accompanied by an expansion of the dI2 progenitor domain [3].
• Previously, we had shown that removal of Pax6 from the Gsh2 mutant background improves the molecular identity of the LGE in these double mutants; however, Raldh3 expression is not improved [4].

Biological context of Gsh2

• The homeobox gene Gsh2 is required for retinoid production in the embryonic mouse telencephalon [4].
• In addition, our data indicate a role for Gsh genes in controlling the size of the LGE precursor pools, since decreasing copies of Gsh2 and Gsh1 alleles results in a notable decrease in precursor cell number, particularly in the subventricular zone [5].
• No telencephalic phenotype was observed in Gsh1 mutants, whereas Gsh2 and Gsh1/2 mutants showed progressively more severe defects in development of neurons derived from the lateral ganglionic eminence (LGE) [6].

Anatomical context of Gsh2

• Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2 [7].
• By contrast, as indicated by both loss- and gain-of-function analysis, Gsh2 expression in the medial ganglionic eminence after E10.5 may negatively regulate Nkx2.1 dependent specification of oligodendrocytes [8].
• One of these genes is Gsh2, whose expression in the forebrain is restricted to the ventral domain [9].
• Gsh2 is required for the repression of Ngn1 and specification of dorsal interneuron fate in the spinal cord [3].
• Moreover, while our analysis suggests that the migration of the ventrally derived interneurons to the developing cerebral cortex is not significantly affected in Gsh2 mutants, there is a distinct delay in the appearance of GABAergic interneurons in the olfactory bulb [9].

Associations of Gsh2 with chemical compounds

• These findings suggest that reduced retinoid production in the Gsh2 mutant contributes to the striatal differentiation defects [4].
• Indeed, RA supplementation of Gsh2 mutants, during the period of striatal neurogenesis, results in a significant increase in DARPP-32 expression [4].

Regulatory relationships of Gsh2

• Gsh2 is expressed in both of the ganglionic eminences while Gsh1 is largely confined to the medial ganglionic eminence [5].
• Patterning of the lateral ganglionic eminence by the Gsh1 and Gsh2 homeobox genes regulates striatal and olfactory bulb histogenesis and the growth of axons through the basal ganglia [6].

Other interactions of Gsh2

• These reciprocal alterations in cortical and striatal progenitor specification lead to the abnormal development of the cortex and striatum observed in Pax6 (small eye) and Gsh2 mutants, respectively [7].
• In its absence, neurogenins are lost from the cortical germinal zone and Gsh2, Mash1 and Dlx genes are found ectopically [7].
• Combinatorial function of the homeodomain proteins Nkx2.1 and Gsh2 in ventral telencephalic patterning [8].
• The Pax6;Gsh2 double mutants possess a larger striatum than the Gsh2 mutants, but the disproportionate reduction in DARPP-32 neurons is not improved [4].
• Concomitant with this normalization, Gsh1 expression is notably expanded in the Gsh2(-/-) LGE [5].

Analytical, diagnostic and therapeutic context of Gsh2

• Whole-mount and serial section in situ hybridizations have been used to better define Gsh-2 expression domains within the developing forebrain, midbrain, and hindbrain [10].

References