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matrix elements while the internal stimuli important for second trimester of gestation and spans into birth
oligodendrocyte formation are transcription factors and and adulthood. [14,15] Specifically, at 9 gestation weeks,
epigenetic regulators. Therefore, studying modulators early OPCs (NG2 and PDGFRα positive) arise from
capable of stimulating OPCs are of paramount the ganglionic eminence and migrate to the cortex
importance and fundamental for future therapies in the following weeks. Late OPCs, which show
concerning inflammatory and neurodegenerative O4 immunoreactivity, are first detected in a small
disorders in which myelin sheaths are affected. percentage at 15 gestation weeks, gaining more density
in midgestation (c. 20‑22 gestation weeks), especially
OLIGODENDROGENESIS FROM OPCs DURING in the subplate layer directly under the cortical plate.
DEVELOPMENT AND IN THE ADULT BRAIN Finally, myelin basic protein‑positive oligodendrocytes
PARENCHYMA are rare at midgestation but show a steady population
growth from that point on. Indeed, the first myelin
During CNS development, and also throughout sheaths can be found around 18 gestation weeks in
adulthood, oligodendrogenesis is derived from OPCs. the thalamus, spreading to the internal capsule at
OPCs are a subtype of glial cell, characterized by the 21 gestation weeks. [15]
expression of the platelet‑derived growth factor receptor
α (PDGFRα), and the neuron‑glial antigen 2 (NG2) Given the nature of oligodendrocyte production,
[6]
proteoglycan [Figure 1]. Other known markers for these one question arises: are the OPCs involved in these
cells are the O4 antigen and the transcription factors different phases functionally equivalent? There is
[7]
Olig1, Olig2, and Nkx 2.2. It should be noted that, these evidence that each phase of OPC production can
markers can be expressed in other cells, a combination lead to the myelination of distinct brain regions, [16]
of markers should be used to unambiguously identify suggesting the existence of functionally different
[1]
OPCs. In the adult brain, OPCs comprise 3‑8% of subpopulations of OPCs that serve separate functions.
the total number of cells and are prevalent in the In fact, a study conducted in mice targeted differentially
[8]
hippocampus and in all layers of the neocortex. [9] ventrally‑derived OPCs (vOPCs) and dorsally‑derived
OPCs (dOPCs), as well as the oligodendrocytes generated
In the developing forebrain of mice, the entire by each class of OPCs (vOLs and dOLs respectively).
oligodendrocyte population is generated from three This study shows that while vOPCs and dOPCs appear
phases of OPC proliferation and migration. The first to have the same electrical properties, their migration
phase occurs at embryonic day 12.5 (E12.5) and and settling patterns are significantly different, to the
consists of a “wave” of OPC production, originated point that vOLs and dOLs populate different forebrain
from ventral ganglionic eminences. [10,11] At E15.5, the and spinal cord regions at different timepoints during
second phase takes place, emerging from the lateral development (for example, while in adulthood the
and caudal ganglionic eminences. [12] Finally, the third corticospinal and rubrospinal tracts are myelinated
phase happens after birth, with origin in the cortex. [12] by dOLs; during early postnatal life, these regions are
These three phases are responsible for the generation actually myelinated by vOLs). [16] On the other hand, it
of most adult oligodendrocytes in mice, which will has been shown that, if one of these subpopulations
migrate and populate most of the future brain. [1] is eliminated, neighboring OPCs of different origins
rapidly migrate and proliferate to generate the regular
In human CNS development, oligodendrocyte number of oligodendrocytes in the mature brain, [12]
differentiation and maturation follow similar paths which could imply that the subpopulations of OPCs
to rodents. [13] This process has its beginning in the are functionally equivalent.

Figure 1: Diagram of the oligodendrocytic lineage progression: from early oligodendrocyte precursor cell to functioning mature myelinating oligodendrocyte

264 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015 265