Cell cycle arrest induced by ectopic expression of p27 is not sufficient to promote oligodendrocyte differentiation.
Oligodendrocyte differentiation is accompanied by dramatic changes in gene expression as well as cell cycle arrest. To determine whether cell cycle arrest is sufficient to induce the changes in cell phenotype associated with differentiation, we inhibited oligodendrocyte precursor proliferation in vitro by overexpressing p27, a cyclin kinase inhibitor, using a recombinant adenovirus. Ectopic expression of p27 efficiently inhibited oligodendrocyte precursor cell division, even in the presence of exogenous mitogens, by blocking the activity of the cyclin-dependent kinase, cdk2. Although the cells had stopped dividing, they did not express galactocerebroside (GalC) or myelin basic protein (MBP), changes associated with oligodendrocyte differentiation, suggesting that they had not differentiated. After removal of exogenous mitogens, however, adenovirus-expressing oligodendrocyte precursors differentiated with a temporal profile similar to that of control, uninfected oligodendrocytes, as indicated by expression of GalC and MBP. We conclude that cell cycle arrest is not sufficient to induce differentiation of dividing oligodendrocyte precursors, and that modulation of additional, as yet unknown, signaling pathways is required for this to occur.
Tang
X M
XM
Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Beesley
J S
JS
Grinspan
J B
JB
Seth
P
P
Kamholz
J
J
Cambi
F
F
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2; D051360:Cyclin-Dependent Kinase 5; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D025521:Tumor Suppressor Proteins
C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495892:Cdk2 protein, rat; C495907:Cdk5 protein, rat; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases