title: Predominant neuronal differentiation of Olig1+ neural progenitors in forebrain cortex biased by β-catenin over-expression.
abstract: Proper neuron-glia ratio is essential for normal brain development and function. Olig1 is a basic helix-loop-helix (bHLH) transcription factor generally used as a lineage tool for oligodendrocyte research in spinal cord. Recent studies have revealed a property of Olig1-positive cells as the common progenitors of GABAergic neurons and oligodendrocytes in the forebrain during embryogenesis, and a stage-dependent regulatory role of Wnt/β-catenin signaling in the differentiation of oligodendrocytes in spinal cord. Given the neurogenic role of Wnt/β-catenin signaling in neural progenitor cells, it is unclear how β-catenin affects the differentiation of Olig1-positive progenitors in brain. In the present study, we investigated the effects of β-catenin over-expression on the differentiation of Olig1-positive progenitors in the forebrain cortex, by using Olig1-Cre:β-cateninEX3 (loxp/+):ROSA-YFP (β-cateninEX3 CKO) mice as compared to Olig1-Cre:ROSA-YFP control. The results showed that in the cortex of Olig1-Cre:ROSA-YFP mice, approximately 28.6% of YFP labeled cells are GFAP-positive, 43.7% are NG2-positive, 23.4% are CC1-positive and 3.2% are NeuN-positive, showing that Olig1-positive cells are multi-potential and mainly gliogenic. However, in the cortex of β-cateninEX3 CKO mice, the percentage of astrocytes generated from Olig1-positive cells decreased dramatically to approximately 2%, NG2-positive cells to 0.4%, and CC1-positive cells to 0.5%. In contrast, the percentage of NeuN-positive cells increased to approximately 96% of YFP-labeled cells. Taken together, our data showed that the gliogenic property of Olig1-positive progenitors in forebrain can be efficiently switched to neurogenic by over-expressing β-catenin, revealing a neurogenic effect of β-catenin in the forebrain Olig1-positive progenitors.
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi'an, Shaanxi 710032, China; Department of Neurology, Xijing Hospital, Fourth Military Medical University, 127 Chang Le Xi Road, Xi'an, Shaanxi 710032, China.
authors.forename: Jialei
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi'an, Shaanxi 710032, China.
authors.forename: Xunyuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi'an, Shaanxi 710032, China.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi'an, Shaanxi 710032, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi'an, Shaanxi 710032, China.
authors.forename: Yuanhang
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Institute of Developmental and Regenerative Biology, Key Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life Sciences, Hangzhou Normal University, Hangzhou310029, China.
authors.forename: Mengsheng
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi'an, Shaanxi 710032, China.
authors.forename: Shengxi
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, 127 Chang Le Xi Road, Xi'an, Shaanxi 710032, China. Electronic address: zhaogang@fmmu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi'an, Shaanxi 710032, China. Electronic address: yazhouw@fmmu.edu.cn.
authors.forename: Ya-Zhou
authors.initials: YZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000166:cytology*; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051176:beta Catenin; C494786:Olig1 protein, mouse
keywords: Neurogenesis; Olig1; β-catenin