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Oligodendrocytes  - Development and Stem Cells


Anatomical Structure and Function of the Oligodendrocytes:

Oligodendrocytes are the myelin-producing glial cells in the central nervous system (CNS). These cells produce myelin, a fatty insulation, which is composed of modified plasma membrane and is essential for rapid propagation of action potentials along the axons of the CNS (brain and spinal cord). In addition, oligodendrocytes provide metabolic support for neurons. One oligodendrocyte can produce up to 40 myelin segments on multiple axons, in contrast to Schwann cells, the glial cells of the peripheral nervous system (PNS) that produce one myelin segment per axon.

All white matter tracts contain oligodendrocytes. Oligodendrocytes are, however, also found in gray matter. Satellite oligodendrocytes, known also as perineuronal oligodendrocytes, are not directly associated with myelin sheaths and are preferentially found in gray matter. Their functions have not been elucidated and have been suggested to regulate ionic homeostasis, much like astrocytes. 

Failure of remyelination or demyelination caused by injury or disease, impairs the rapid conduction of action potentials, resulting in axonal degeneration in demyelinating diseases such as multiple sclerosis.

Embryonic and Postnatal Development of the Oligodendrocytes:

All CNS neurons and glial cells (oligodendrocytes and astrocytes) develop from neuroepithelial progenitor cells located in the ventricular zone (VZ), the wall of the embryonic neural tube. The oligodendrocytes derive from oligodendrocyte precursor cells (OPCs), which arise from multiple restricted regions of the ventricular zone in the developing CNS, including the telencephalon, diencephalon, mesencephalon, rhombencephalon and spinal cord.

This database maps oligodendrocytes derived from the dorsoventral telencephalon and spinal cord. This models the development of oligodendrocytes derived from the diencephalon, mesencephalon and rhombencephalon, which have yet to be mapped.

In the developing spinal cord, the OPCs first arise from a specialized domain of the ventral ventricular zone called the motor neuron progenitor domain (pMN), defined by expression of Olig2. This domain generates 80% of the spinal oligodendrocytes. Later, secondary sources develop in the dorsal spinal cord (dP3-5 domains). 

In the developing telencephalon, the OPCs originate from the ventricular zone in three distinct waves. The first wave directly arise from Nkx2.1+ progenitor cells and appears, at E12 in mice, in the anterior entopeduncular area (AEP) and the medial ganglionic eminence (MGE) domains located in the ventral (basal) telencephalon.  The cells then migrate into the cortex at E16 and postnatally mature into myelinating oligodendrocytes. A second wave arises from Gsx2+ progenitor cells at around E14.5, in the lateral ganglionic eminence (LGE) and caudal ganglionic eminence (CGE) domains. The third wave arises close to birth, from Emx1+ progenitor cells within the cortex in the dorsal telencephalon. Most of the early-born oligodendrocytes disappear after birth, thus the cortex-derived oligodendrocytes present the majority of the oligodendrocytes in the adult cortex.

The oligodendrocytes continue to born during adulthood. These cells arise from the brain parenchyma and from precursor cells located in the sub-ventricular zone (SVZ). In response to demyelinating lesions, the OPCs proliferate and differentiate into mature oligodendrocytes that restore myelin sheaths.  However, these cells do not migrate extensively.