[en] 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 LID 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. (C) 2006 Wiley-Liss, Inc.
Aguirre AA, Chittajallu R, Belachew S, et al. 2004. NG2-expressing cells in the subventricular zone are Type C-like cells and contribute to interneuron generation in the postnatal hippocampus. J Cell Biol 165:575-589.
Ahlgren SC, Wallace H, Bishop J, et al. 1997. Effects of thyroid hormone on embryonic oligodendrocyte precursor cell development in vivo and in vitro. Mol Cell Neurosci 9:420-432.
Akazawa C, Sasai Y, Nakanishi S, et al. 1992. Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system. J Biol Chem 267:21879-21885.
Aleem E, Berthet C, Kaldis P. 2004. Cdk2 as a master of S phase entry: Fact or fake? Cell Cycle 3:35-37.
Aleem E, Kiyokawa H, Kaldis P. 2005. Cdc2-cyclin E complexes regulate the G1/S phase transition. Nat Cell Biol 7:831-836.
Arnett HA, Fancy SP, Alberta JA, et al. 2004. bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS. Science 306:2111-2115.
Assoian RK. 2004. Stopping and going with p27(kip1). Dev Cell 6:458-459.
Barres BA, Lazar MA, Raff MC. 1994. A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development. Development 120:1097-1108.
Belachew S, Aguirre AA, Wang H, et al. 2002. Cyclin-dependent kinase-2 controls oligodendrocyte progenitor cell cycle progression and is downregulated in adult oligodendrocyte progenitors. J Neurosci 22:8553-8562.
Belachew S, Chittajallu R, Aguirre AA, et al. 2003. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. J Cell Biol 161: 169-186.
Belachew S, Yuan X, Gallo V. 2001. Unraveling oligodendrocyte origin and function by cell-specific transgenesis. Dev Neurosci 23:287-298.
Benezra R, Davis RL, Lockshon D, et al. 1990. The protein Id: A negative regulator of helix-loop-helix DNA binding proteins. Cell 61: 49-59.
Berthet C, Aleem E, Coppola V, et al. 2003. Cdk2 knockout mice are viable. Curr Biol 13:1775-1785.
Bertrand N, Castro DS, Guillemot F. 2002. Proneural genes and the specification of neural cell types. Nat Rev Neurosci 3:517-530.
Besson A, Gurian-West M, Schmidt A, et al. 2004. p27Kip1 modulates cell migration through the regulation of RhoA activation. Genes Dev 18:862-876.
Billon N, Jolicoeur C, Tokumoto Y, et al. 2002. Normal timing of oligodendrocyte development depends on thyroid hormone receptor α 1 (TRα1). EMBO J 21:6452-6460.
Billon N, Terrinoni A, Jolicoeur C, et al. 2004. Roles for p53 and p73 during oligodendrocyte development. Development 131:1211-1220.
Billon N, Tokumoto Y, Forrest D, et al. 2001. Role of thyroid hormone receptors in timing oligodendrocyte differentiation. Dev Biol 235:110-120.
Blakemore WF, Keirstead HS. 1999. The origin of remyelinating cells in the CNS. J Neuroimmunol 98:69-76.
Bogler O, Noble M. 1994. Measurement of time in oligodendrocyte-type-2 astrocyte (O-2A) progenitors is a cellular process distinct from differentiation or division. Dev Biol 162:525-538.
Bolton WE, Freeman JW, Mikulka WR, et al. 1994. Expression of proliferation-associated antigens (PCNA, p120, p145) during the reentry of GO cells into the cell cycle. Cytometry 17:66-74.
Bornstein G, Bloom J, Sitry-Shevah D, et al. 2003. Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase. J Biol Chem 278:25752-25757.
Carroll WM, Jennings AR. 1994. Early recruitment of oligodendrocyte precursors in CNS demyelination. Brain 117 (Part 3):563-578.
Casaccia-Bonnefil P. 2000. Cell death in the oligodendrocyte lineage: A molecular perspective of life/death decisions in development and disease. Glia 29:124-135.
Casaccia-Bonnefil P, Hardy RJ, Teng KK, et al. 1999. Loss of p27Kip1 function results in increased proliferative capacity of oligodendrocyte progenitors but unaltered timing of differentiation. Development 126:4027-4037.
Casaccia-Bonnefil P, Tikoo R. Kiyokawa H, et al. 1997. Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1. Genes Dev 11:2335-2346.
Chan CL, Wigley CB, Berry M. 1990. Oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells from neonatal and adult rat optic nerve differ in their responsiveness to platelet-derived growth factor. Brain Res Dev Brain Res 55:275-282.
Chang A, Nishiyama A, Peterson J, et al. 2000. NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions. J Neurosci 20:6404-6412.
Chang A, Tourtellotte WW, Rudick R, et al. 2002. Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med 346:165-173.
Cheng M, Olivier P, Diehl JA, et al. 1999. The p21(Cip1) and p27(Kipl) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J 18: 1571-1583.
Compston A, Coles A. 2002. Multiple sclerosis. Lancet 359:1221-1231.
Coqueret O. 2003. New roles for p21 and p27 cell-cycle inhibitors: A function for each cell compartment? Trends Cell Biol 13:65-70.
Cunningham JJ, Roussel MF. 2001. Cyclin-dependent kinase inhibitors in the development of the CNS. Cell Growth Differ 12:387-396.
Dawson MR, Levine JM, Reynolds R. 2000. NG2-expressing cells in the CNS: Are they oligodendroglial progenitors? J Neurosci Res 61:471-479.
Durand B, Fero ML, Roberts JM, et al. 1998. p27Kip1 alters the response of cells to mitogen and is part of a cell-intrinsic timer that arrests the cell cycle and initiates differentiation. Curr Biol 8:431-440.
Durand B, Gao FB, Raff M. 1997. Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J 16:306-317.
Dyson N. 1998. The regulation of E2F by pRB-family proteins. Genes Dev 12:2245-2262.
Eizenberg O, Faber-Elman A, Gottlieb E, et al. 1996. p53 plays a regulatory role in differentiation and apoptosis of CNS-associated cells. Mol Cell Biol 16:5178-5185.
Engel U, Wolswijk G. 1996. Oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells derived from adult rat spinal cord: In vitro characteristics and response to PDGF, bFGF and NT-3. Glia 16:16-26.
Fero ML, Rivkin M, Tasch M, et al. 1996. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice. Cell 85: 733-744.
Ffrench-Constant C, Raff MC. 1986. Proliferating bipotential glial progenitor cells in adult rat optic nerve. Nature 319:499-502.
Fisher AL, Ohsako S, Gaudy M. 1996. The WRPW motif of the hairy-related basic helix-loop-helix repressor proteins acts as a 4-amino-acid transcription repression and protein-protein interaction domain. Mol Cell Biol 16:2670-2677.
Franklin DS, Godfrey VL, Lee H, et al. 1998. CDK inhibitors p18(INK4c) and p27(Kip1) mediate two separate pathways to collaboratively suppress pituitary tumorigenesis. Genes Dev 12:2899-2911.
Franklin RJ. 2002. Why does remyelination fail in multiple sclerosis? Nat Rev Neurosci 3:705-714.
Franklin RJ, Gilson JM, Blakemore WF. 1997. Local recruitment of remyelinating cells in the repair of demyelination in the CNS. J Neurosci Res 50:337-344.
Friessen AJ, Miskimins WK, Miskimins R. 1997. Cyclin-dependent kinase inhibitor p27kip1 is expressed at high levels in cells that express a myelinating phenotype. J Neurosci Res 50: 373-382.
Fu H, Qi Y, Tan M, et al. 2002. Dual origin of spinal oligodendrocyte progenitors and evidence for the cooperative role of Olig2 and Nkx2.2 in the control of oligodendrocyte differentiation. Development 129:681-693.
Gallo V, Ghiani CA. 2000. Glutamate receptors in glia: New cells, new inputs and new functions. Trends Pharm Sci 21:252-258.
Gao FB, Apperly J, Raff M. 1998. Cell-intrinsic timers and thyroid hormone regulate the probability of cell-cycle withdrawal and differentiation of oligodendrocyte precursor cells. Dev Biol 197:54-66.
Gao FB, Durand B, Raff M. 1997. Oligodendrocyte precursor cells count time but not cell divisions before differentiation. Curr Biol 7:152-155.
Geng Y, Yu Q, Sicinska E, et al. 2003. Cyclin E ablation in the mouse. Cell 114:431-443.
Gensert JM, Goldman JE. 1997. Endogenous progenitors remyelinate demyelinated axons in the adult CNS. Neuron 19:197-203.
Ghiani CA, Eisen AM, Yuan XQ, et al. 1999a. Neurotransmitter receptor activation triggers p27(Kip1) and p21(CIP1) accumulation and G(1) cell cycle arrest in oligodendrocyte progenitors. Development 126:1077-1090.
Ghiani CA, Gallo V. 2001. Inhibition of cyclin E-cyclin-dependent kinase 2 complex formation and activity is associated with cell cycle arrest and withdrawal in oligodendrocyte progenitor cells. J Neurosci 21:1274-1282.
Ghiani CA, Yuan XQ, Eisen AM, et al. 1999b. Voltage-activated K+ channels and membrane depolarization regulate accumulation of the cyclin-dependent kinase inhibitors p277(Kip1) and p21 (CIP1) in glial progenitor cells. J Neurosci 19:5380-5392.
Giaccia AJ, Kastan MB. 1998. The complexity of p53 modulation: Emerging patterns from divergent signals. Genes Dev 12:2973-2983.
Grbavec D, Stifani S. 1996. Molecular interaction between TLE1 and the carboxyl-terminal domain of HES-1 containing the WRPW motif. Biochem Biophys Res Commun 223:701-705.
Guillemot F. 1999. Vertebrate bHLH genes and the determination of neuronal fates. Exp Cell Res 253:357-364.
Hartwell LH, Kastan MB. 1994. Cell cycle control and cancer. Science 266:1821-1828.
Hengst L, Gopfert U, Lashuel HA, et al. 1998. Complete inhibition of Cdk/cyclin by one molecule of p21(Cip1). Genes Dev 12:3882-3888.
Huang Z, Tang XM, Cambi F. 2002. Down-regulation of the retinoblastoma protein (rb) is associated with rat oligodendrocyte differentiation. Mol Cell Neurosci 19:250-262.
Hyde-Dunn J, Jones GE. 1997. Visualization of cell replication using antibody to proliferating cell nuclear antigen. Methods Mol Biol 75:341-347.
Jirawatnotai S, Aziyu A, Osmundson EO, et al. 2004. Cdk4 is indispensable for postnatal proliferation of the anterior pituitary. J Biol Chem 279:51100-51106.
John GR, Shankar SL, Shafit-Zagardo B, et al. 2002. Multiple sclerosis: Re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat Med 8:1115-1121.
Johnson JE, Birren SJ, Anderson DJ. 1990. Two rat homologues of Drosophila achaete-scute specifically expressed in neuronal precursors. Nature 46:858-861.
King RW, Deshaies RJ, Peters JM, et al. 1996. How proteolysis drives the cell cycle. Science 274:1652-1659.
Kiyokawa H, Kineman RD, Manova-Todorova KO, et al. 1996. Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1). Cell 85:721-732.
Knockaert M, Greengard P, Meijer L. 2002. Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci 23:417-425.
Kondo T, Raff M. 2000a. Basic helix-loop-helix proteins and the timing of oligodendrocyte differentiation. Development 127:2989-2998.
Kondo T, Raff M. 2000b. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289:1754-1757.
Kondo T, Raff M. 2000c. The Id4 HLH protein and the timing of oligodendrocyte differentiation. EMBO J 19:1998-2007.
Kozar K, Ciemerych MA, Rebel VI, et al. 2004. Mouse development and cell proliferation in the absence of d-cyclins. Cell 118:477-491.
LaBaer J, Garrett MD, Stevenson LF, et al. 1997. New functional activities for the p21 family of CDK inhibitors. Genes Dev 11:847-862.
Levine JM, Reynolds R, Fawcett JW. 2001. The oligodendrocyte precursor cell in health and disease. Trends Neurosci 24:39-47.
Levrero M, De LV, Costanzo A, et al. 2000. The p53/p63/p73 family of transcription factors: Overlapping and distinct functions. J Cell Sci 113 (Part 10):1661-1670.
Liu R, Cai J, Hu X, et al. 2003. Region-specific and stage-dependent regulation of Olig gene expression and oligodendrogenesis by Nkx6.1 homeodomain transcription factor. Development 130:6221-6231.
Louis JC, Magal E, Muir D, et al. 1992. CG-4, a new bipotential glial cell line from rat brain, is capable of differentiating in vitro into either mature oligodendrocytes or type-2 astrocytes. J Neurosci Res 31:193-204.
Lu QR, Cai L, Rowitch D, et al. 2001. Ectopic expression of Olig1 promotes oligodendrocyte formation and reduces neuronal survival in developing mouse cortex. Nat Neurosci 4:973-974.
Lu QR, Sun T, Zhu Z, et al. 2002. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 109:75-86.
Lu QR, Yuk D, Alberta JA, et al. 2000. Sonic hedgehog-Regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian CNS. Neuron 25:317-329.
Maeda Y, Solanky M, Menonna J, et al. 2001. Platelet-derived growth factor-α receptor-positive oligodendroglia are frequent in multiple sclerosis lesions. Ann Neurol 49:776-785.
Malek NP, Sundberg H, McGrew S, et al. 2001. A mouse knock-in model exposes sequential proteolytic pathways that regulate p27Kip1 in G1 and S phase. Nature 413:323-327.
Malumbres M, Sotillo R, Santamaria D, et al. 2004. Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6. Cell 118:493-504.
Matsumoto Y, Maller JL. 2004. A centrosomal localization signal in cyclin E required for Cdk2-independent S phase entry. Science 306:885-888.
Meijer L, Borgne A, Mulner O, et al. 1997. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem 243:527-536.
Morgan DO. 1995. Principles of CDK regulation. Nature 374:131-134.
Morgan DO. 1997. Cyclin-dependent kinases: Engines, clocks, and microprocessors. Annu Rev Cell Dev Biol 13:261-291.
Nakayama K, Ishida N, Shirane M, et al. 1996. Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 85:707-720.
Nakayama K, Nagahama H, Minamishima YA, et al. 2000. Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication. EMBO J 19:2069-2081.
Nakayama KI, Hatakeyama S, Nakayama K. 2001. Regulation of the cell cycle at the G1-S transition by proteolysis of cyclin E and p27Kip1. Biochem Biophys Res Commun 282:853-860.
Nguyen L, Benson A, Hong JIT, et al. 2006. p27Kip1 independently promotes neuronal differentiation and migration in the cerebral cortex. Genes Dev Published May 16, 2006, 10.1101/gad.377106.
Nguyen L, Malgrange B, Rocher V, et al. 2003. Chemical inhibitors of cyclin-dependent kinases control proliferation, apoptosis and differentiation of oligodendroglial cells. Int J Dev Neurosci 21:321-326.
Noble M, Murray K. 1984. Purified astrocytes promote the in vitro division of a bipotential glial progenitor cell. EMBO J 3:2243-2247.
Noble M, Murray K, Stroobant P, et al. 1988. Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell. Nature 333:560-562.
Norton JD. 2000. ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. J Cell Sci 113 (Part 22):3897-3905.
Norton JD, Deed RW, Craggs G, et al. 1998. Id helix-loop-helix proteins in cell growth and differentiation. Trends Cell Biol 8:58-65.
Nunes MC, Roy NS, Keyoung HM, et al. 2003. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med 9:439-447.
Ohtsubo M, Theodoras AM, Schumacher J, et al. 1995. Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol Cell Biol 15:2612-2624.
Ortega S, Prieto I, Odajima J, et al. 2003. Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat Genet 35:25-31.
Pardee AB. 1974. A restriction point for control of normal animal cell proliferation. Proc Natl Acad Sci USA 71:1286-1290.
Pardee AB. 1989. G1 events and regulation of Cell proliferation. Science 246:603-608.
Parisi T, Beck AR, Rougier N, et al. 2003. Cyclins E1 and E2 are required for endoreplication in placental trophoblast giant cells. EMBO J 22: 4794-4803.
Parras CM, Galli R, Britz O, et al. 2004. Mash1 specifies neurons and oligodendrocytes in the postnatal brain. EMBO J 23:4495-4505.
Pfeiffer SE, Warington AE, Bansal R. 1993. The oligodendrocyte and its many cellular processes. Trends Cell Biol 3:191-197.
Planas-Silva MD, Weinberg RA. 1997. The restriction point and control of cell proliferation. Curr Opin Cell Biol 9:768-772.
Qi Y, Cai J, Wu Y, et al. 2001. Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor. Development 128:2723-2733.
Raff MC, Abney ER, Fok-Seang J. 1985. Reconstitution of a developmental clock in vitro: A critical role for astrocytes in the timing of oligodendrocyte differentiation. Cell 42:61-69.
Raff MC, Lillien LE, Richardson WD, et al. 1988. Platelet-derived growth factor from astrocytes drives the clock that times oligodendrocyte development in culture. Nature 333:562-565.
Reynolds R, Hardy R. 1997. Oligodendroglial progenitors labeled with the O4 antibody persist in the adult rat cerebral cortex in vivo. J Neurosci Res 47:455-470.
Roberts JM. 1999. Evolving ideas about cyclins. Cell 98:129-132.
Ross SE, Greenberg ME, Stiles CD. 2003. Basic helix-loop-helix factors in cortical development. Neuron 39:13-25.
Rowitch DH, Lu QR, Kessaris N, et al. 2002. An 'oligarchy' rules neural development. Trends Neurosci 25:417-422.
Russo AA, Jeffrey PD, Patten AK, et al. 1996. Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature 382:325-331.
Samanta J, Kessler JA. 2004. Interactions between ID and OLIG proteins mediate the inhibitory effects of BMP4 on oligodendroglial differentiation. Development 131:4131-4142.
Sasai Y, Kageyama R, Tagawa Y, et al. 1992. Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split. Genes Dev 6:2620-2634.
Sausville EA, Zaharevitz D, Gussio R, et al. 1999. Cyclin-dependent kinases: Initial approaches to exploit a novel therapeutic target. Pharmacol Ther 82:285-292.
Schuurmans C, Guillemot F. 2002. Molecular mechanisms underlying cell fate specification in the developing telencephalon. Curr Opin Neurobiol 12:26-34.
Setoguchi T, Kondo T. 2004. Nuclear export of OLIG2 in neural stem cells is essential for ciliary neurotrophic factor-induced astrocyte differentiation. J Cell Biol 166:963-968.
Sherr CJ. 1994a. The ins and outs of RB: Coupling gene expression to the cell cycle clock. Trends Cell Biol 4:15-18.
Sherr CJ. 1996. Cancer cell cycles. Science 274: 1672-1677.
Sherr CJ, Roberts JM. 1995. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 9:1149-1163.
Sherr CJ, Roberts JM. 1999. CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev 13:1501-1512.
Sim FJ, Zhao C, Penderis J, et al. 2002. The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci 22:2451-2459.
Stevaux O, Dyson NJ. 2002. A revised picture of the E2F transcriptional network and RB function. Curr Opin Cell Biol 14:684-691.
Stidworthy MF, Genoud S, Li WW, et al. 2004. Notch1 and Jagged1 are expressed after CNS demyelination, but are not a major rate-determining factor during remyelination. Brain 127:1928-1941.
Stolt CC, Lommes P, Sock E, et al. 2003. The Sox9 transcription factor determines glial fate choice in the developing spinal cord. Genes Dev 17:1677-1689.
Sun T, Dong H, Wu L, et al. 2003. Cross-repressive interaction of the Olig2 and Nkx2.2 transcription factors in developing neural tube associated with formation of a specific physical complex. J Neurosci 23:9547-9556.
Sun T, Echelard Y, Lu R, et al. 2001. Olig bHLH proteins interact with homeodomain proteins to regulate cell fate acquisition in progenitors of the ventral neural tube. Curr Biol 11:1413-1420.
Takebayashi H, Yoshida S, Sugimori M, et al. 2000. Dynamic expression of basic helix-loop-helix Olig family members: Implication of Olig2 in neuron and oligodendrocyte differentiation and identification of a new member, Olig3. Mech Dev 99:143-148.
Tang DG, Tokumoto YM, Apperly JA, et al. 2001. Lack of replicative senescence in cultured rat oligodendrocyte precursor cells. Science 291: 868-871.
Tang DG, Tokumoto YM, Raff MC. 2000. Long-term culture of purified postnatal oligodendrocyte precursor cells. Evidence for an intrinsic maturation program that plays out over months. J Cell Biol 148:971-984.
Tang XM, Beesley JS, Grinspan JB, et al. 1999. Cell cycle arrest induced by ectopic expression of p27 is not sufficient to promote oligodendrocyte differentiation. J Cell Biochem 76:270-279.
Tang XM, Strocchi P, Cambi F. 1998. Changes in the activity of cdk2 and cdk5 accompany differentiation of rat primary oligodendrocytes. J Cell Biochem 68:128-137.
Temple S, Raff MC. 1985. Differentiation of a bipotential glial progenitor cell in a single cell microculture. Nature 313:223-225.
Temple S, Raff MC. 1986. Clonal analysis of oligodendrocyte development in culture: Evidence for a developmental clock that counts cell divisions. Cell 44:773-779.
Tikoo R, Casaccia-Bonnefil P, Chao MV, et al. 1997. Changes in cyclin-dependent kinase 2 and p27kip1 accompany glial cell differentiation of central glia-4 cells. J Biol Chem 272: 442-447.
Tikoo R, Osterhout DJ, Casaccia-Bonnefil P, et al. 1998. Ectopic expression of p27Kip1 in oligodendrocyte progenitor cells results in cell-cycle growth arrest. J Neurobiol 36:431-440.
Tokumoto YM, Apperly JA, Gao FB, et al. 2002. Post transcriptional regulation of p18 and p27 Cdk inhibitor proteins and the timing of oligodendrocyte differentiation. Dev Biol 245: 224-234.
Tokumoto YM, Durand B, Raff MC. 1999. An analysis of the early events when oligodendrocyte precursor cells are triggered to differentiate by thyroid hormone, retinoic acid, or PDGF withdrawal. Dev Biol 213:327-339.
Tokumoto YM, Tang DG, Raff MC. 2001. Two molecularly distinct intracellular pathways to oligodendrocyte differentiation: Role of a p53 family protein. EMBO J 20:5261-5268.
Tsai LH, Lees E, Faha B, et al. 1993. The cdk2 kinase is required for the G1-to-S transition in mammalian cells. Oncogene 8:1593-1602.
Tyers M, Jorgensen P. 2000. Proteolysis and the cell cycle: With this RING I do thee destroy. Curr Opin Genet Dev 10:54-64.
van den Heuvel S, Harlow E. 1993. Distinct roles for cyclin-dependent kinases in cell cycle control. Science 262:2050-2054.
van Heyningen P, Calver AR, Richardson WD. 2001. Control of progenitor cell number by mitogen supply and demand. Curr Biol 11: 232-241.
Vlach J, Hennecke S, Amati B. 1997. Phosphorylation-dependent degradation of the cyclin-dependent kinase inhibitor p27. EMBO J 16: 5334-5344.
Wang S, Sdrulla A, Johnson JE, et al. 2001. A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte development. Neuron 29:603-614.
Wang S, Sdrulla AD, diSibio G, et al. 1998. Notch receptor activation inhibits oligodendrocyte differentiation. Neuron 21:63-75.
Wang Y, Penfold S, Tang X, et al. 1999. Deletion of the Cul1 gene in mice causes arrest in early embryogenesis and accumulation of cyclin E. Curr Biol 9:1191-1194.
Weinberg RA. 1995. The retinoblastoma protein and cell cycle control. Cell 81:323-330.
Welcker M, Singer J, Loeb KR, et al. 2003. Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol Cell 12: 381-392.
Wolswijk G. 1998. Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J Neurosci 18:601-609.
Wolswijk G, Noble M. 1989. Identification of an adult-specific glial progenitor cell. Development 105:387-400.
Wolswijk G, Noble M. 1992. Cooperation between PDGF and FGF converts slowly dividing O-2Aadult progenitor cells to rapidly dividing cells with characteristics of O-2Aperinatal progenitor cells. J Cell Biol 118:889-900.
Xin M, Yue T, Ma Z, et al. 2005. Myelinogenesis and axonal recognition by oligodendrocytes in brain are uncoupled in Olig1-null mice. J Neurosci 25:1354-1365.
Yang A, Kaghad M, Caput D, et al. 2002. On the shoulders of giants: p63, p73 and the rise of p53. Trends Genet 18:90-95.
Yang A, McKeon F. 2000. P63 and P73: P53 mimics, menaces and more. Nat Rev MoI Cell Biol 1:199-207.
Yew PR. 2001. Ubiquitin-mediated proteolysis of vertebrate G1- and S-phase regulators. J Cell Physiol 187:1-10.
Yuan X, Chittajallu R, Belachew S, et al. 2002. Expression of the green fluorescent protein in the oligodendrocyte lineage: A transgenic mouse for developmental and physiological studies. J Neurosci Res 70:529-545.
Zebedee Z, Hara E. 2001. Id proteins in cell cycle control and cellular senescence. Oncogene 20:8317-8325.
Zetterberg A, Larsson O, Wiman KG. 1995. What is the restriction point? Curr Opin Cell Biol 7:835-842.
Zezula J, Casaccia-Bonnefil P, Ezhevsky SA, et al. 2001. p21cip1 is required for the differentiation of oligodendrocytes independently of cell cycle withdrawal. EMBO Rep 2:27-34.
Zhou Q, Anderson DJ. 2002. The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification. Cell 109: 61-73.
Zhou Q, Choi G, Anderson DJ. 2001. The bHLH transcription factor Olig2 promotes oligodendrocyte differentiation in collaboration with Nkx2.2. Neuron 31:791-807.
Zhou Q, Wang S, Anderson DJ. 2000. Identification of a novel family of oligodendrocyte lineage-specific basic helix-loop-helix transcription factors. Neuron 25:331-343.