The Yin and Yang of cell cycle progression and differentiation in the oligodendroglial lineage.
In white matter disorders such as leukodystrophies (LD), periventricular leucomalacia (PVL), or multiple sclerosis (MS), the hypomyelination or the remyelination failure by oligodendrocyte progenitor cells involves errors in the sequence of events that normally occur during development when progenitors proliferate, migrate through the white matter, contact the axon, and differentiate into myelin-forming oligodendrocytes. Multiple mechanisms underlie the eventual progressive deterioration that typifies the natural history of developmental demyelination in LD and PVL and of adult-onset demyelination in MS. Over the past few years, pathophysiological studies have mostly focused on seeking abnormalities that impede oligodendroglial maturation at the level of migration, myelination, and survival. In contrast, there has been a strikingly lower interest for early proliferative and differentiation events that are likely to be equally critical for white matter development and myelin repair. This review highlights the Yin and Yang principles of interactions between intrinsic factors that coordinately regulate progenitor cell division and the onset of differentiation, i.e. the initial steps of oligodendrocyte lineage progression that are obviously crucial in health and diseases.
Nguyen
Laurent
L
Developmental Neurobiology Unit, Center for Cellular and Molecular Neuroscience, University of Liège, C.H.U. Sart Tilman, B36, 4000 Liège, Belgium.
Borgs
Laurence
L
Vandenbosch
Renaud
R
Mangin
Jean-Marie
JM
Beukelaers
Pierre
P
Moonen
Gustave
G
Gallo
Vittorio
V
Malgrange
Brigitte
B
Belachew
Shibeshih
S
D000328:Adult; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D019927:Cyclin E / Q000502:physiology; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology; D003711:Demyelinating Diseases / Q000235:genetics / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000235:genetics / Q000473:pathology; D009103:Multiple Sclerosis / Q000473:pathology; D009186:Myelin Sheath / Q000235:genetics / Q000473:pathology; D009836:Oligodendroglia / Q000473:pathology*; D010766:Phosphorylation; D013234:Stem Cells / Q000473:pathology
D019927:Cyclin E; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051357:Cyclin-Dependent Kinase 2