Involvement of the Olig2 transcription factor in cholinergic neuron development of the basal forebrain

Abstract

Cholinergic neurons, which express choline acetyltransferase (ChAT), are a major neuron subset generated in the basal forebrain. Areas presumed to be sites of origin of cholinergic neurons are roughly demarcated by expression of Olig2, a basic helix-loop-helix transcription factor, which includes the medial ganglionic eminence, septal area, and anterior entopeduncular/preoptic area. In the present study, we examined the involvement of Olig2 in cholinergic differentiation. When the Olig2-expressing cells at E12.5 were permanently modified to express the lacZ or EGFP gene by tamoxifen-induced Cre-mediated recombination, the cells marked by reporter gene expression were widely distributed in the basal forebrain by E18.5, some of which expressed neuronal markers. We showed that a small number of cells were double-positive for ChAT and X-gal or EGFP in almost all cases. In addition, the number of ChAT+ cells was reduced to 60% in the Olig2 knockout mouse basal forebrain. No evidence of elevated apoptosis or reduced proliferation was observed in the knockout mouse forebrain. The present study provides the first direct evidence for involvement of the Olig2 gene in cholinergic differentiation in the basal forebrain.

Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms

“…Olig2 is a bHLH transcriptional repressor protein that plays essential roles in the lineage specification of progenitor cells into neuronal subtypes (somatic motor neurons and forebrain cholinergic neurons) and oligodendrocytes during central nervous system development [60][61][62][63][64][65][66]. At early embryonic stages, one key role of Olig2 is to maintain progenitor cells in a replication-competent state [67].…”

Maternal Undernutrition Induces the Expression of Hypoxia-Related Genes in the Fetal Brain

“…Thus, the colocalization of oligodendrocyte transcription factor 2 (Olig.2), a marker specific for OPC (Furusho et al 2006), and HIF1α was evaluated by immunostaining. The coronal sections were fixed with 4% paraformaldehyde (Wako Pure Chemical Industries, Ltd, Osaka, Japan) for 30 min.…”

Cholinergic Circuits and Signaling in the Pathophysiology of Schizophrenia

“…Forebrain cholinergic neurons arise early in telencephalic development (~E10 in mouse which approximately corresponds to gestational day 40 in humans; Clancy et al, 2001) in the medial ganglionic eminence, a ventricular/subventricular neurogenic zone that appears as a thickening along the ventral/medial wall of the ventricle (Brady et al, 1989;Furusho, 2006;Marin et al, 2000;Olsson et al, 1998;Semba et al, 1988). Presumptive forebrain projection cholinergic neurons migrate from the MGE (and possibly from the anterior entopeduncular/preoptic area) radially to take up locations in basal forebrain nuclei (medial septum, magnocellular nucleus, diagonal band of Broca), whereas the striatal cholinergic interneurons migrate tangentially from the MGE, occupying dispersed sites throughout the striatal plate.…”

“…In particular, the basics of a cholinergic transcription factor code are emerging. A variety of experimental approaches has demonstrated that expression of several transcription factors is important (Mash 1, Olig2, Lmx7, Lmx8) or essential (Nkx2.1) for generating forebrain cholinergic neurons (Bachy and Retaux, 2006;Furusho et al, 2006;Marin et al, 2000;Mori et al, 2004;Zhao et al, 2003). Thus, the combined expression of these factors, and their target genes, probably accounts for much of the intrinsic identity of the cholinergic phenotype.…”