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J Neurosci
2005 Nov 16;2546:10773-85. doi: 10.1523/JNEUROSCI.3207-05.2005.
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PBK/TOPK, a proliferating neural progenitor-specific mitogen-activated protein kinase kinase.
Dougherty JD
,
Garcia AD
,
Nakano I
,
Livingstone M
,
Norris B
,
Polakiewicz R
,
Wexler EM
,
Sofroniew MV
,
Kornblum HI
,
Geschwind DH
.
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We performed genomic subtraction coupled to microarray-based gene expression profiling and identified the PDZ (postsynaptic density-95/Discs large/zona occludens-1)-binding kinase/T-LAK (lymphokine-activated killer T cell) cell originating protein kinase (PBK/TOPK) as a gene highly enriched in neural stem cell cultures. Previous studies have identified PBK/TOPK as a mitogen-activated protein kinase (MAPK) kinase that phosphorylated P38MAPK but with no known expression or function in the nervous system. First, using a novel, bioinformatics-based approach to assess cross-correlation in large microarray datasets, we generated the hypothesis of a cell-cycle-related role for PBK/TOPK in neural cells. We then demonstrated that both PBK/TOPK and P38 are activated in a cell-cycle-dependent manner in neuronal progenitor cells in vitro, and inhibition of this pathway disrupts progenitor proliferation and self-renewal, a core feature of progenitors. In vivo, PBK/TOPK is expressed in rapidly proliferating cells in the adult subependymal zone (SEZ) and early postnatal cerebellar external granular layer. Using an approach based on transgenically targeted ablation and lineage tracing in mice, we show that PBK/TOPK-positive cells in the SEZ are GFAP negative but arise from GFAP-positive neural stem cells during adult neurogenesis. Furthermore, ablation of the adult stem cell population leads to concomitant loss of PBK/TOPK-positive cells in the SEZ. Together, these studies demonstrate that PBK/TOPK is a marker for transiently amplifying neural progenitors in the SEZ. Additionally, they suggest that PBK/TOPK plays an important role in these progenitors, and further implicates the P38MAPK pathway in general, as an important regulator of progenitor proliferation and self-renewal.
Abe,
Cloning and expression of a novel MAPKK-like protein kinase, lymphokine-activated killer T-cell-originated protein kinase, specifically expressed in the testis and activated lymphoid cells.
2000, Pubmed
Abe,
Cloning and expression of a novel MAPKK-like protein kinase, lymphokine-activated killer T-cell-originated protein kinase, specifically expressed in the testis and activated lymphoid cells.
2000,
Pubmed
Aguirre,
NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus.
2004,
Pubmed
Altman,
Postnatal development of the cerebellar cortex in the rat. I. The external germinal layer and the transitional molecular layer.
1972,
Pubmed
Anderson,
Stem cells and pattern formation in the nervous system: the possible versus the actual.
2001,
Pubmed
Bush,
Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice.
1999,
Pubmed
Campos,
Activation of p38 mitogen-activated protein kinase during normal mitosis in the developing retina.
2002,
Pubmed
Capela,
LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal.
2002,
Pubmed
Dennis,
DAVID: Database for Annotation, Visualization, and Integrated Discovery.
2003,
Pubmed
Doetsch,
Subventricular zone astrocytes are neural stem cells in the adult mammalian brain.
1999,
Pubmed
Doetsch,
Regeneration of a germinal layer in the adult mammalian brain.
1999,
Pubmed
Doetsch,
EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells.
2002,
Pubmed
Doetsch,
Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain.
1997,
Pubmed
Easterday,
Neural progenitor genes. Germinal zone expression and analysis of genetic overlap in stem cell populations.
2003,
Pubmed
Eisen,
Cluster analysis and display of genome-wide expression patterns.
1998,
Pubmed
Freije,
Gene expression profiling of gliomas strongly predicts survival.
2004,
Pubmed
Furuta,
Glutamate transporter protein subtypes are expressed differentially during rat CNS development.
1997,
Pubmed
Gage,
Mammalian neural stem cells.
2000,
Pubmed
Gallagher,
Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase.
1997,
Pubmed
Galli,
Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma.
2004,
Pubmed
Garcia,
GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain.
2004,
Pubmed
Gaudet,
Characterization of PDZ-binding kinase, a mitotic kinase.
2000,
Pubmed
Geschwind,
A genetic analysis of neural progenitor differentiation.
2001,
Pubmed
Goldman,
Fate determination and migration of progenitors in the postnatal mammalian CNS.
1997,
Pubmed
Guillemot,
Analysis of the role of basic-helix-loop-helix transcription factors in the development of neural lineages in the mouse.
1995,
Pubmed
Hemmati,
Cancerous stem cells can arise from pediatric brain tumors.
2003,
Pubmed
Hosack,
Identifying biological themes within lists of genes with EASE.
2003,
Pubmed
Ignatova,
Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro.
2002,
Pubmed
Imura,
The predominant neural stem cell isolated from postnatal and adult forebrain but not early embryonic forebrain expresses GFAP.
2003,
Pubmed
Karsten,
Global analysis of gene expression in neural progenitors reveals specific cell-cycle, signaling, and metabolic networks.
2003,
Pubmed
Krishan,
Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining.
1975,
Pubmed
Lee,
Isolation of neural stem cells from the postnatal cerebellum.
2005,
Pubmed
Lendahl,
CNS stem cells express a new class of intermediate filament protein.
1990,
Pubmed
Li,
Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection.
2001,
Pubmed
Lie,
Neurogenesis in the adult brain: new strategies for central nervous system diseases.
2004,
Pubmed
Lindvall,
Stem cell therapy for human neurodegenerative disorders-how to make it work.
2004,
Pubmed
Lu,
Control of cell divisions in the nervous system: symmetry and asymmetry.
2000,
Pubmed
Luskin,
Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone.
1993,
Pubmed
Maslov,
Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice.
2004,
Pubmed
Matsumoto,
Characterization of a MAPKK-like protein kinase TOPK.
2004,
Pubmed
Menezes,
The division of neuronal progenitor cells during migration in the neonatal mammalian forebrain.
1995,
Pubmed
Migheli,
A cell cycle alteration precedes apoptosis of granule cell precursors in the weaver mouse cerebellum.
1999,
Pubmed
Miki,
Delineating developmental and metabolic pathways in vivo by expression profiling using the RIKEN set of 18,816 full-length enriched mouse cDNA arrays.
2001,
Pubmed
Milosevic,
Progenitors in the postnatal cerebellar white matter are antigenically heterogeneous.
2002,
Pubmed
Morshead,
The ablation of glial fibrillary acidic protein-positive cells from the adult central nervous system results in the loss of forebrain neural stem cells but not retinal stem cells.
2003,
Pubmed
Morshead,
Disguising adult neural stem cells.
2004,
Pubmed
Morshead,
Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells.
1994,
Pubmed
Morshead,
In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain.
1998,
Pubmed
Murray,
Widespread defects in the primary olfactory pathway caused by loss of Mash1 function.
2003,
Pubmed
Nakano,
Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation.
2005,
Pubmed
Ohnuma,
Neurogenesis and the cell cycle.
2003,
Pubmed
Palmer,
Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS.
1999,
Pubmed
Parras,
Mash1 specifies neurons and oligodendrocytes in the postnatal brain.
2004,
Pubmed
Ren,
Genome-wide location and function of DNA binding proteins.
2000,
Pubmed
Reynolds,
Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.
1992,
Pubmed
Simons-Evelyn,
PBK/TOPK is a novel mitotic kinase which is upregulated in Burkitt's lymphoma and other highly proliferative malignant cells.
2001,
Pubmed
Singh,
Identification of a cancer stem cell in human brain tumors.
2003,
Pubmed
Terskikh,
From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs.
2001,
Pubmed
Tsurimoto,
PCNA binding proteins.
1999,
Pubmed
Wechsler-Reya,
Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog.
1999,
Pubmed
Whitfield,
Identification of genes periodically expressed in the human cell cycle and their expression in tumors.
2002,
Pubmed
Yuryev,
Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis.
2003,
Pubmed
Zhao,
PDZ-binding kinase participates in spermatogenesis.
2001,
Pubmed