Oligodendrocytes originate in a restricted zone of the embryonic ventral neural tube defined by DM-20 mRNA expression

Abstract

Products of the PLP gene, proteolipid protein and its isoform DM-20, are the most abundant proteins in CNS myelin, and are markers of the oligodendrocyte, the myelin-forming cell in the CNS. The DM-20 transcript has previously been reported to be expressed in newborn oligodendrocyte progenitor cells and during embryonic development. We have therefore used a DM-20 cRNA probe to follow, by in situ hybridization, the oligodendrocyte lineage during embryonic development. DM-20-expressing cells were first detected at E9.5 in the ventricular germinal layer of the laterobasal plate of the diencephalon. At E14.5, DM-20+ cells had largely disappeared from the diencephalic ventricular germinal layer and had colonized the ventral mantle layer at the posterior part of the basal diencephalon. Between E17.5 and P1, the number of DM-20+ cells increased and progressively invaded the major white matter tracts. In the hindbrain, DM-20+ cells appeared at E12.5 in the caudal part of the rhombencephalon, and at E14.5 all along the ventral spinal cord. Between E14.5 and P1, DM-20+ cells progressively colonized, first ventrally then dorsally, all the spinal cord and more extensively the white matter tracts. At E14.5, a large gap separated, rostrally, the medullary columns from the mantle layer cells in the prosencephalon, suggesting that oligodendrocytes in the mid- and forebrain originate from a different pool of precursors than in the rhombencephalon and the spinal cord. Together, these observations suggest that expression of the DM-20 transcript is an early marker of commitment to the oligodendrocyte lineage, and that oligodendrocyte precursors originate in a ventrally restricted region.

Separate Proteolipid Protein/DM20 Enhancers Serve Different Lineages and Stages of Development

“…5A). Because oligodendrocyte progenitors are emerging within the E14.5 neural tube (Pringle and Richardson, 1993) and because such progenitors express DM20 (Timsit et al, 1995), we considered it probable that such transgene-expressing cells were oligodendrocyte progenitors. To confirm this possibility, cross sections were processed to reveal both ␤-galactosidase and the well established oligodendrocyte progenitor marker PDGFR␣.…”

“…DM20 transcripts are detected in the blastocyst (Skoff et al, 2004), seminiferous tubules, myocardial cells, thymus, and spleen (Campagnoni et al, 1992;Pribyl et al, 1996). In the mouse nervous system, DM20 is expressed in neural progenitors as early as embryonic day 9.5 (E9.5) and in oligodendrocyte progenitors by E14.5 (Timsit et al, 1992(Timsit et al, , 1995Yu et al, 1994;Fanarraga et al, 1996;Dickinson et al, 1997;Spassky et al, 1998;Gudz et al, 2006). DM20 also accumulates in multiple glial cell types, including olfactory bulb ensheathing cells (OECs), spinal and autonomic ganglia satellite cells, Schwann cells, and enteric glia (Griffiths et al, 1989(Griffiths et al, , 1995Puckett et al, 1987;Dickinson et al, 1997).…”

A neuropathological analysis of experimental autoimmune encephalomyelitis with predominant brain stem and cerebellar involvement and differences between active and passive induction

“…One possibility is that the target antigen, PLP [190][191][192][193][194][195][196][197][198][199][200][201][202][203][204][205][206][207][208][209] , varies in its distribution or accessibility within the CNS. Although it is known that PLP is distributed throughout CNS myelin, there is evidence that oligodendrocytes that myelinate different regions of the CNS can originate at different times during development [32] and that the biochemical and physical properties of oligodendrocytes differ, depending on where they are situated in the CNS [3,18]. Another possibility is that the C3H/HeJ strain of mice differs from other strains in the concentration of professional antigen-presenting cells or in the expression of major histocompatibility complex molecules in certain areas.…”

nkx2.2apromotes specification and differentiation of a myelinating subset of oligodendrocyte lineage cells in zebrafish

“…Therefore, we next tested expression of two genes commonly used as markers of oligodendrocyte differentiation. In rodents, RNA for the DM20 splicing variant of PLP, which encodes proteolipid protein, is expressed in newly formed OPCs, well before myelination (Timsit et al, 1995;Dickinson et al, 1996;Peyron et al, 1997). Consequently, PLP/DM20 expression marks oligodendrocyte lineage cells as they progress from progenitor to myelinating stages (Baumann and Pham-Dinh, 2001).…”