 |
||||
|
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, August 1, 2000, 20(15):5756-5763
A Role for p27/Kip1 in the Control of Cerebellar Granule Cell Precursor Proliferation
Kazuhiro Miyazawa1, 2, Toshiyuki Himi3, Veronica Garcia3, Hisakazu Yamagishi2, Shigeaki Sato1, and Yasuki Ishizaki1 1 Department of Hygiene, Kobe University School of Medicine, Chuo-ku, Kobe 650-0017, Japan, 2 Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-0841, Japan, and 3 Department of Physiological Chemistry, Postgraduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8549, Japan
During development, control of proliferation of neuronal precursor cells plays a crucial role in determining the number of neurons. Proliferation is driven by mitogens, but how it is terminated remains a mystery. In this study, we examined the role of cyclin-dependent kinase inhibitors in the control of proliferation of cerebellar granule cell precursors (GCPs). Among the inhibitors we examined, only p27/Kip1 (p27) was expressed at significant levels in cells of the granule cell lineage in the developing and adult cerebellum. In developing cerebella, p27 was expressed in the external germinal layer (the deeper regions), the molecular layer, and the granule layer. In adult cerebella, p27 was expressed in the cells of the granule layer. We isolated and purified GCPs from cerebella of developing mice and examined their bromodeoxyuridine (BrdU) uptake and p27 expression at various times. We found that there was an inverse correlation between BrdU uptake and p27 expression. Even in the presence of saturating amounts of Sonic hedgehog, a potent mitogen, the cells eventually stopped dividing and differentiated, expressing p27 strongly. We also examined mice in which one or both copies of the p27 gene have been inactivated by targeted gene disruption and found that their cerebella were larger than those of wild-type mice. In cell cultures, GCPs prepared from p27-deficient mice showed enhanced proliferation compared with GCPs from wild-type mice. Taken together, these results suggest that there is an intracellular mechanism that stops GCP division and causes GCPs to differentiate and that p27 is part of this mechanism.
Key words: cyclin-dependent kinase inhibitor; p27; cerebellum; cerebellar granule cells; proliferation; cell cycle
Copyright © 2000 Society for Neuroscience 0270-6474/00/20155756-08$05.00/0
This article has been cited by other articles:
X. Li, X. Tang, B. Jablonska, A. Aguirre, V. Gallo, and M. B. Luskin
p27KIP1 Regulates Neurogenesis in the Rostral Migratory Stream and Olfactory Bulb of the Postnatal Mouse
J. Neurosci., March 4, 2009; 29(9): 2902 - 2914.
[Abstract] [Full Text] [PDF]
J. D. Kessler, H. Hasegawa, S. N. Brun, B. A. Emmenegger, Z.-J. Yang, J. W. Dutton, F. Wang, and R. J. Wechsler-Reya
N-myc alters the fate of preneoplastic cells in a mouse model of medulloblastoma
Genes & Dev., January 15, 2009; 23(2): 157 - 170.
[Abstract] [Full Text] [PDF]
O. Ayrault, F. Zindy, J. Rehg, C. J. Sherr, and M. F. Roussel
Two Tumor Suppressors, p27Kip1 and Patched-1, Collaborate to Prevent Medulloblastoma
Mol. Cancer Res., January 1, 2009; 7(1): 33 - 40.
[Abstract] [Full Text] [PDF]
L. L. Collins, M. A. Williamson, B. D. Thompson, D. P. Dever, T. A. Gasiewicz, and L. A. Opanashuk
2,3,7,8-Tetracholorodibenzo-p-Dioxin Exposure Disrupts Granule Neuron Precursor Maturation in the Developing Mouse Cerebellum
Toxicol. Sci., May 1, 2008; 103(1): 125 - 136.
[Abstract] [Full Text] [PDF]
B. Carletti and F. Rossi
Neurogenesis in the Cerebellum
Neuroscientist, February 1, 2008; 14(1): 91 - 100.
[Abstract] [PDF]
S. Schmetsdorf, U. Gartner, and T. Arendt
Constitutive Expression of Functionally Active Cyclin-Dependent Kinases and Their Binding Partners Suggests Noncanonical Functions of Cell Cycle Regulators in Differentiated Neurons
Cereb Cortex, August 1, 2007; 17(8): 1821 - 1829.
[Abstract] [Full Text] [PDF]
C. Vaillant, O. Michos, S. Orolicki, F. Brellier, S. Taieb, E. Moreno, H. Te, R. Zeller, and D. Monard
Protease nexin 1 and its receptor LRP modulate SHH signalling during cerebellar development
Development, May 1, 2007; 134(9): 1745 - 1754.
[Abstract] [Full Text] [PDF]
M. D. Muzumdar, L. Luo, and H. Zong
From the Cover: Modeling sporadic loss of heterozygosity in mice by using mosaic analysis with double markers (MADM)
PNAS, March 13, 2007; 104(11): 4495 - 4500.
[Abstract] [Full Text] [PDF]
J. Pogoriler, K. Millen, M. Utset, and W. Du
Loss of cyclin D1 impairs cerebellar development and suppresses medulloblastoma formation
Development, October 1, 2006; 133(19): 3929 - 3937.
[Abstract] [Full Text] [PDF]
F. Zindy, P. S. Knoepfler, S. Xie, C. J. Sherr, R. N. Eisenman, and M. F. Roussel
N-Myc and the cyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 coordinately regulate cerebellar development
PNAS, August 1, 2006; 103(31): 11579 - 11583.
[Abstract] [Full Text] [PDF]
T. Uziel, F. Zindy, S. Xie, Y. Lee, A. Forget, S. Magdaleno, J. E. Rehg, C. Calabrese, D. Solecki, C. G. Eberhart, et al.
The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation
Genes & Dev., November 15, 2005; 19(22): 2656 - 2667.
[Abstract] [Full Text] [PDF]
Y. Choi, P. R. Borghesani, J. A. Chan, and R. A. Segal
Migration from a Mitogenic Niche Promotes Cell-Cycle Exit
J. Neurosci., November 9, 2005; 25(45): 10437 - 10445.
[Abstract] [Full Text] [PDF]
B. Argenti, R. Gallo, L. Di Marcotullio, E. Ferretti, M. Napolitano, S. Canterini, E. De Smaele, A. Greco, M. T. Fiorenza, M. Maroder, et al.
Hedgehog Antagonist RENKCTD11 Regulates Proliferation and Apoptosis of Developing Granule Cell Progenitors
J. Neurosci., September 7, 2005; 25(36): 8338 - 8346.
[Abstract] [Full Text] [PDF]
H.-C. Park, J. Boyce, J. Shin, and B. Appel
Oligodendrocyte Specification in Zebrafish Requires Notch-Regulated Cyclin-Dependent Kinase Inhibitor Function
J. Neurosci., July 20, 2005; 25(29): 6836 - 6844.
[Abstract] [Full Text] [PDF]
L.-M. Sturla, C. W. Cowan, L. Guenther, R. C. Castellino, J. Y.H. Kim, and S. L. Pomeroy
A Novel Role for Extracellular Signal-Regulated Kinase 5 and Myocyte Enhancer Factor 2 in Medulloblastoma Cell Death
Cancer Res., July 1, 2005; 65(13): 5683 - 5689.
[Abstract] [Full Text] [PDF]
L. Perez-Martinez and D. M. Jaworski
Tissue Inhibitor of Metalloproteinase-2 Promotes Neuronal Differentiation by Acting as an Anti-Mitogenic Signal
J. Neurosci., May 18, 2005; 25(20): 4917 - 4929.
[Abstract] [Full Text] [PDF]
J. D. Corrales, G. L. Rocco, S. Blaess, Q. Guo, and A. L. Joyner
Spatial pattern of sonic hedgehog signaling through Gli genes during cerebellum development
Development, November 15, 2004; 131(22): 5581 - 5590.
[Abstract] [Full Text] [PDF]
S. Blaess, D. Graus-Porta, R. Belvindrah, R. Radakovits, S. Pons, A. Littlewood-Evans, M. Senften, H. Guo, Y. Li, J. H. Miner, et al.
{beta}1-Integrins Are Critical for Cerebellar Granule Cell Precursor Proliferation
J. Neurosci., March 31, 2004; 24(13): 3402 - 3412.
[Abstract] [Full Text] [PDF]
T. Okano-Uchida, T. Himi, Y. Komiya, and Y. Ishizaki
Cerebellar granule cell precursors can differentiate into astroglial cells
PNAS, February 3, 2004; 101(5): 1211 - 1216.
[Abstract] [Full Text] [PDF]
A. M. Kenney, H. R. Widlund, and D. H. Rowitch
Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors
Development, January 1, 2004; 131(1): 217 - 228.
[Abstract] [Full Text] [PDF]
S. Marino, D. Hoogervoorst, S. Brandner, and A. Berns
Rb and p107 are required for normal cerebellar development and granule cell survival but not for Purkinje cell persistence
Development, August 1, 2003; 130(15): 3359 - 3368.
[Abstract] [Full Text] [PDF]
S. Marino, P. Krimpenfort, C. Leung, H. A. G. M. van der Korput, J. Trapman, I. Camenisch, A. Berns, and S. Brandner
PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum
Development, March 9, 2003; 129(14): 3513 - 3522.
[Abstract] [Full Text] [PDF]
G. Estivill-Torrus, H. Pearson, V. van Heyningen, D. J. Price, and P. Rashbass
Pax6 is required to regulate the cell cycle and the rate of progression from symmetrical to asymmetrical division in mammalian cortical progenitors
Development, March 3, 2003; 129(2): 455 - 466.
[Abstract] [Full Text] [PDF]
J. Luo, Y. Sun, H. Lin, Y. Qian, Z. Li, S. S. Leonard, C. Huang, and X. Shi
Activation of JNK by Vanadate Induces a Fas-associated Death Domain (FADD)-dependent Death of Cerebellar Granule Progenitors in Vitro
J. Biol. Chem., February 7, 2003; 278(7): 4542 - 4551.
[Abstract] [Full Text] [PDF]
C. Angley, M. Kumar, K. J. Dinsio, A. K. Hall, and R. E. Siegel
Signaling by Bone Morphogenetic Proteins and Smad1 Modulates the Postnatal Differentiation of Cerebellar Cells
J. Neurosci., January 1, 2003; 23(1): 260 - 268.
[Abstract] [Full Text] [PDF]
C. G. Eberhart
Medulloblastoma in Mice Lacking p53 and PARP: All Roads Lead To Gli
Am. J. Pathol., January 1, 2003; 162(1): 7 - 10.
[Full Text] [PDF]
P. J. Simpson, I. Miller, C. Moon, A. L. Hanlon, D. J. Liebl, and G. V. Ronnett
Atrial Natriuretic Peptide Type C Induces a Cell-Cycle Switch from Proliferation to Differentiation in Brain-Derived Neurotrophic Factor- or Nerve Growth Factor-Primed Olfactory Receptor Neurons
J. Neurosci., July 1, 2002; 22(13): 5536 - 5551.
[Abstract] [Full Text] [PDF]
J. Aruga, T. Inoue, J. Hoshino, and K. Mikoshiba
Zic2 Controls Cerebellar Development in Cooperation with Zic1
J. Neurosci., January 1, 2002; 22(1): 218 - 225.
[Abstract] [Full Text] [PDF]
S. M. Duplan, Y. Theoret, and R. Kenigsberg
Antitumor Activity of Fibroblast Growth Factors (FGFs) for Medulloblastoma May Correlate with FGF Receptor Expression and Tumor Variant
Clin. Cancer Res., January 1, 2002; 8(1): 246 - 257.
[Abstract] [Full Text] [PDF]
M.-E. Legrier, A. Ducray, A. Propper, M. Chao, and A. Kastner
Cell Cycle Regulation during Mouse Olfactory Neurogenesis
Cell Growth Differ., December 1, 2001; 12(12): 591 - 601.
[Abstract] [Full Text] [PDF]
J. J. Cunningham and M. F. Roussel
Cyclin-dependent Kinase Inhibitors in the Development of the Central Nervous System
Cell Growth Differ., August 1, 2001; 12(8): 387 - 396.
[Full Text] [PDF]
E. A. Maher, F. B. Furnari, R. M. Bachoo, D. H. Rowitch, D. N. Louis, W. K. Cavenee, and R. A. DePinho
Malignant glioma: genetics and biology of a grave matter
Genes & Dev., June 1, 2001; 15(11): 1311 - 1333.
[Full Text] [PDF]
|
|
|
|
 |
|