Involvement of the Olig2 transcription factor in cholinergic neuron development of the basal forebrain.
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.
Department of Physiological Sciences, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan.
Miki
M
Furusho
Katsuhiko
K
Ono
Hirohide
H
Takebayashi
Noritaka
N
Masahira
Tetsushi
T
Kagawa
Kazuyo
K
Ikeda
Kazuhiro
K
Ikenaka
D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D060850:LIM-Homeodomain Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D011247:Pregnancy; D016548:Prosencephalon / Q000196:embryology* / Q000378:metabolism*; D014157:Transcription Factors
D051792:Basic Helix-Loop-Helix Proteins; D002795:Choline O-Acetyltransferase; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D014157:Transcription Factors; C112960:LIM homeobox protein 8; C512773:Olig2 protein, mouse