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Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage

Abstract

The developmental origin of oligodendrocyte progenitors (OLPs) in the forebrain has been controversial. We now show, by Cre-lox fate mapping in transgenic mice, that the first OLPs originate in the medial ganglionic eminence (MGE) and anterior entopeduncular area (AEP) in the ventral forebrain. From there, they populate the entire embryonic telencephalon including the cerebral cortex before being joined by a second wave of OLPs from the lateral and/or caudal ganglionic eminences (LGE and CGE). Finally, a third wave arises within the postnatal cortex. When any one population is destroyed at source by the targeted expression of diphtheria toxin, the remaining cells take over and the mice survive and behave normally, with a normal complement of oligodendrocytes and myelin. Thus, functionally redundant populations of OLPs compete for space in the developing brain. Notably, the embryonic MGE- and AEP-derived population is eliminated during postnatal life, raising questions about the nature and purpose of the competition.

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Figure 1: Three successive waves of OLs generated from distinct precursor populations at different times during forebrain development.
Figure 2: The embryonic Nkx2.1-derived OL lineage is rapidly eliminated during postnatal life.
Figure 3: Design and activity of a Cre-inducible Dta transgene under Sox10 transcriptional control.
Figure 4: Genetic ablation of region-specific OL populations reveals functional redundancy and compensation among the different lineages.
Figure 5: Transient delay in accumulation of OLPs after ablation of the LGE-CGE–derived population in Gsh2-Cre/Sox10-DTA mice.

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Acknowledgements

We thank our colleagues at the Wolfson Institute for Biomedical Research and elsewhere for discussion, technical help and advice—especially M. Fruttiger, U. Dennehy and R. Taveira-Marques. We thank I. Maxwell for supplying the DTA plasmid. This work was funded by the UK Medical Research Council, the Wellcome Trust Functional Genomics Initiative and a Wellcome Trust Prize Studentship (M.F.).

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Correspondence to Nicoletta Kessaris or William D Richardson.

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Cre deleter lines. (PDF 780 kb)

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Kessaris, N., Fogarty, M., Iannarelli, P. et al. Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat Neurosci 9, 173–179 (2006). https://doi.org/10.1038/nn1620

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