The evolution of Olig genes and their roles in myelination

Abstract

One of the special attributes of vertebrates is their myelinated nervous system. By increasing the conduction velocity of axons, myelin allows for increased body size, rapid movement and a large and complex brain. In the central nervous system (CNS), oligodendrocytes (OLs) are the myelin-forming cells. The transcription factors OLIG1 and OLIG2, master regulators of OL development, presumably also played a seminal role during the evolution of the genetic programme leading to myelination in the CNS. From the available ontogenetic and phylogenetic data we attempt to reconstruct the evolutionary events that led to the emergence of the Olig gene family and speculate about the links between Olig genes, their specific cis-regulatory elements and myelin evolution. In addition, we report a putative myelin basic protein (MBP) ancestor in the lancelet Branchiostoma floridae, which lacks compact myelin. The lancelet 'Mbp' gene lacks the OLIG1/2- and SOX10-binding sites that characterize vertebrate Mbp homologs, raising the possibility that insertion of cis-regulatory elements might have been involved in evolution of the myelinating programme.

Altered Expression of Oligodendrocyte and Neuronal Marker Genes Predicts the Clinical Onset of Autoimmune Encephalomyelitis and Indicates the Effectiveness of Multiple Sclerosis–Directed Therapeutics

“…1, data not shown). Mbp encodes myelin basic protein, a major myelin component, whereas Olig2 is a transcription factor that controls oligodendrocyte development (31). Similarly, expression of all selected neuron-specific genes, Nrg1, Ninj1, Snap25, and Grin1, was markedly downregulated at the presymptomatic time point and, as with the myelin genes, expression continued to decrease until the peak of disease (Fig.…”

“…The altered expression of oligodendrocyte genes also can enhance neuroinflammation, as shown in mice conditionally deficient for the peroxisome gene peroxin-5 in oligodendrocytes (45). Finally, downregulation of Olig2, a master regulator of oligodendrocyte development (31), might compromise myelin repair in later stages of EAE. Overall, reduced expression of Mbp and other myelin genes from very early in EAE might enhance the susceptibility of both myelin and axons to immunemediated damage and limit the potential for remyelination in later stages of disease.…”

Detailed Expression Analysis of Regulatory Genes in the Early Developing Human Neural Tube

“…2E, H) was successively reduced, encompassing a few cell layers at the end of neurogenic stages (Fig. 2F) [ 29,30], such as Sox9, PDGFRa, Sox10, and Olig1 (Fig. 2N).…”

The Evolution of Myelin: Theories and Application to Human Disease

“…There was probably a high risk to Osteostraci from predatory arthropods [104]. Fish escape using axial muscles, which are innervated by motorneurons which progress only for short distances outside the spinal cord (notably, modern jawless fish without myelin do not exhibit fast escape reflexes).…”