Oligodendrocyte wars

Abstract

Oligodendrocyte precursors first arise in a restricted ventral part of the embryonic spinal cord and migrate laterally and dorsally from there. Later, secondary sources develop in the dorsal cord. Normally, the ventrally-derived precursors compete with and suppress their dorsal counterparts. There are also ventral and dorsal sources in the forebrain, but here the more dorsal precursors prevail and the ventral-most lineage is eliminated during postnatal life. How do the different populations compete and what is the outcome of the competition? Do different embryonic origins signify different functional subgroups of oligodendrocyte?

Figure 1

Progenitor domains in the embryonic spinal cord and the cell types that they generate. Neurons are formed before glia - astrocytes (astros) and oligodendrocyte precursors (OLPs). In general, OLPs are formed before astrocytes and ventral cell types before dorsal. Also shown are the expression domains of transcription factors mentioned in the text. Dotted lines indicate that the expression domain boundaries shift during development, in the direction of the small arrows – e.g. Nkx2.2 expression expands dorsally and Dbx1 expression contracts. Approximately 85% of all spinal cord oligodendrocytes are generated from pMN and the remainder from more dorsal progenitor domains. It is not known whether astrocytes are also generated from pMN but, if so, they are probably produced in small numbers relative to oligodendrocytes. FP, floor plate; RP, roof plate; dP1-dP6, dorsal progenitor domains; pMN and p0-p3, ventral progenitor domains.

Figure 2

Origins and migration of oligodendrocyte precursors in the rodent cervical spinal cord (left) and telencephalon (right). In the mouse spinal cord, approximately 85% of oligodendrocyte precursors are generated from pMN in the ventral VZ, starting around E12.5. Around E15, a secondary wave of precursors starts to be generated in more dorsal regions– by trans-differentiation of radial glia. In the telencephalon, the ventral-most precursors in the MGE are produced from around E12.5, the LGE-derived precursors start to be produced a few days later and the cortex-derived precursors mainly after birth. Diagram not to scale.

Figure 3

Ventral origin of Pdgfra-positive oligodendrocyte precursors. In chick cervical spinal cord, Pdgfra+ precursors are derived exclusively from the dorsal part of the Nkx2.2-expressing domain, within the area of overlap between Nkx2.2 and Olig2 – a hybrid p3/pMN domain. In mouse cervical spinal cord, in contrast, they initially arise within the Olig2+ pMN domain, outside the dorsal limit of Nkx2.2+ expression (arrows). Later, after dorsal expansion of Nkx2.2 expression, they appear to arise within both the (Nkx2.2+, Olig2+) and (Nkx2.2--, Olig2+) domains. In both chicks and mice, oligodendrocyte precursors up-regulate Nkx2.2 as they differentiate into myelinating oligodendrocytes in the white matter . Left panel: combined Nkx2.2 immunolabelling (green fluorescence) and Pdgfra in situ hybridization (black). Right panel: double in situ hybridization for Nkx2.2 (brown reaction product) and Pdgfra (blue). In the right panel, we assume that the blue Pdgfra+ cells in the floor plate region are oligodendrocyte precursors that have migrated ventrally from the ventral VZ, although it is also possible that they arose within the floor plate itself.