Regulation of the timing of oligodendrocyte differentiation: mechanisms and perspectives

Abstract

Axonal myelination is an essential process for normal functioning of vertebrate central nervous system. Proper formation of myelin sheaths around axons depends on the timely differentiation of oligodendrocytes. It was observed that the differentiation occurs on a predictable schedule both in culture and during development. However, the timing mechanisms for oligodendrocyte differentiation during normal development have not been fully uncovered. Recent studies have identified a large number of regulatory factors including the cell-intrinsic factors and extracellular signals that could control the timing of oligodendrocyte differentiation. Here we provide a mechanistic and critical review on the timing control of oligodendrocyte differentiation.

High-Content Phenotypic Screening and Triaging Strategy to Identify Small Molecules Driving Oligodendrocyte Progenitor Cell Differentiation

“…Similarly, in a screen 24 using the mouse CNS-derived Oli-neu cell line, a compound from the Library of Pharmacologically Active Compounds (LOPAC; PD174265) active in the primary assay (performed on collagen-coated plates in the absence of growth factors) turned out later to be dependent on the absence of PDGF. Assay formats, such as choice or origin of cell type or technical execution, 22,25,26 can therefore be expected to select for different types of compounds and ultimately different mechanisms of action. It should also be noted that whole cell-based phenotypic approaches lend themselves to the very pertinent study of synergism of diverse compound classes found in screening, or compounds that affect other relevant related cell types in co-cultures (e.g., for OPC co-cultured with neurons and/or astrocytes).…”

TAPP1 inhibits the differentiation of oligodendrocyte precursor cells via suppressing the Mek/Erk pathway

“…OLs are developmentally generated through the differentiation and maturation of OL precursor cells (OPCs) [3,4] . Impairment of OL function and CNS myelin can cause devastating neurological disorders such as multiple sclerosis [1,5,6] , and psychiatric disorders such as schizophrenia and depression [7] .…”

Dose-dependent regulation of oligodendrocyte specification by β-catenin signaling

“…Although some of these conflicts could be explained by the finding that Wnt/β-catenin signaling regulates oligodendrocyte development in a stage-and region-specific manner [4,[8][9][10] , its role in the differentiation of oligoden drocytes remains elusive. To address whether Wnt/β-catenin signaling regulates oligodendrocyte development in a dose-dependent manner, we generated mice with different muta tions of β-catenin in early OLPs, β-catenin ΔExon3/+ , β-catenin ΔExon2-6/ΔExon2-6 , and β-catenin ΔExon3/ΔExon2-6 .…”