The Lateral Ganglionic Eminence Does Not Generate Cortical Oligodendrocytes

Jialin Li
Feihong Yang
Yu Tian
Ziwu Wang
Dashi Qi
Zhengang Yang
Jiangang Song
Jing Ding
Xin Wang author has email address
Zhuangzhi Zhang author has email address

State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, and Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
Department of Anesthesiology, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Center for Clinical Research and Translational Medicine, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, P.R. China

https://doi.org/10.7554/eLife.94317.1

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Figures and data

Fate mapping of LGE-derived OPCs by combining IUE with a Cre recombinase-dependent IS reporter
(A) In situ hybridization showing Pdgfra expression from E13.5 to P0. Arrowheads indicated the Pdgfra⁺cell migration stream from the MGE/AEP to the cortex.
(B) Scheme of the IS reporter lines.
(C) Experimental schedule to trace LGE-derived OPCs.
(D) Representative coronal sections showing the distribution of tdT⁺ cells.
(E) tdT⁺ cells expressed NeuN but not OLIG2, SOX10, PDGFRA or NG2 in the cortex. In contrast, the tdT⁺ cells expressed all of these markers (OLIG2, SOX10, PDGFRA, NG2 and NeuN) in the striatum.
(F) Fate mapping of LGE-derived cells at P0. tdT⁺ cells expressed SOX10 and SOX9 in the striatum at P49.

Fate mapping of LGE-derived OPCs by combining IUE with PiggyBac transposon system
(A) Schematic of the PiggyBac transposon reporter system used in this study.
(B) The experimental workflow.
(C) Representative coronal sections showing the distribution of GFP⁺ cells at E18.5.
(D) GFP⁺ cells expressed NeuN but not glial cell markers, such as OLIG2, SOX10 and PDGFRA in the cortex. However, GFP⁺ cells expressed NeuN, OLIG2, SOX10 and PDGFRA in the striatum.
(E) GFP⁺ cells expressed NeuN but not glial cell markers, such as OLIG2, SOX10 and PDGFRA in the cortex and GFP⁺ cells expressed NeuN, OLIG2, SOX10 and PDGFRA in the striatum at P10.

An exclusion strategy showed that cortical OPCs do not come from the LGE/CGE
(A) Scheme of the H2B-GFP reporter lines.
(B) Experimental design of the exclusion strategy to trace the lineage of LGE RGCs.
(C) Representative coronal sections showing the traced cells in the forebrain. The majority of SOX10- and PDGFRA-positive cells were GFP⁺ cells in the cortex at P10.
(D-E) The pie chart shows that the percentage of LGE/dMGE-derived cortical OPCs was approximately 3%. N = 6 mice per group.
(F) Many GFP⁺ cells expressed SOX10 and PDGFRA in the striatum at P10.
(G) Nearly all SOX10 and PDGFRA expressed GFP in the cortex at P0.
(H-I) The pie chart shows that the percentage of LGE/dMGE-derived cortical OPCs was less than 3%. N = 6 mice per group.

The MGE may be the sole ventral source of cortical OPCs
(A) The CRISPR/Cas9 technique was used to generate an Olig2 conditional knockout allele.
(B) Experimental design for the generation of Olig2-NCKO mice.
(C-D) The expression of SOX10 and PDGFRA was significantly reduced in the cortex of Olig2-NCKO mice compared with that of control mice.
(E) The number of SOX10- and PDGFRA-positive cells was significantly reduced in Olig2-NCKO mice compared with control mice. Student’s t-test, **P <.01, ***P <.001, n ≥ 5 mice per group, mean ± SEM.
(F) Few PDGFRA-positive cells were detected in the MGE/AEP of the Olig2-NCKO mice.
(G) A new model of the developmental origins of cortical OPCs.

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