spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 7 July 2004
doi: 10.1242/dev.01204

Development 131, 3805-3819 (2004)
Published by The Company of Biologists 2004
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Figures
Right arrow All Versions of this Article:
dev.01204v1
131/15/3805    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ferri, A. L. M.
Right arrow Articles by Nicolis, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ferri, A. L. M.
Right arrow Articles by Nicolis, S. K.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain

Anna L. M. Ferri1, Maurizio Cavallaro1, Daniela Braida2, Antonello Di Cristofano3, Annalisa Canta1, Annamaria Vezzani4, Sergio Ottolenghi1, Pier Paolo Pandolfi3, Mariaelvina Sala2, Silvia DeBiasi5 and Silvia K. Nicolis1,*

1 Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
2 Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milano, via Vanvitelli 32, 20129 Milano, Italy
3 Cancer Biology and Genetics Program, and Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 110, New York, NY 10021, USA
4 Department of Neuroscience, `Mario Negri' Institute of Pharmacological Research, via Eritrea 62, 20157 Milano, Italy
5 Department of Biomolecular Sciences and Biotechnology, University of Milano, via Celoria 26, 20133 Milano, Italy

* Author for correspondence (e-mail: silvia.nicolis{at}unimib.it)

Accepted 2 April 2004

In many species, the Sox2 transcription factor is a marker of the nervous system from the beginning of its development, and we have previously shown that Sox2 is expressed in embryonic neural stem cells. It is also expressed in, and is essential for, totipotent inner cell mass stem cells and other multipotent cell lineages, and its ablation causes early embryonic lethality. To investigate the role of Sox2 in the nervous system, we generated different mouse mutant alleles: a null allele (Sox2ß-geo `knock-in'), and a regulatory mutant allele (Sox2{Delta}ENH), in which a neural cell-specific enhancer is deleted. Sox2 is expressed in embryonic early neural precursors of the ventricular zone and, in the adult, in ependyma (a descendant of the ventricular zone). It is also expressed in the vast majority of dividing precursors in the neurogenic regions, and in a small proportion of differentiated neurones, particularly in the thalamus, striatum and septum. Compound Sox2ß-geo/{Delta}ENH heterozygotes show important cerebral malformations, with parenchymal loss and ventricle enlargement, and L-dopa-rescuable circling behaviour and epilepsy. We observed striking abnormalities in neurones; degeneration and cytoplasmic protein aggregates, a feature common to diverse human neurodegenerative diseases, are observed in thalamus, striatum and septum. Furthermore, ependymal cells show ciliary loss and pathological lipid inclusions. Finally, precursor cell proliferation and the generation of new neurones in adult neurogenic regions are greatly decreased, and GFAP/nestin-positive hippocampal cells, which include the earliest neurogenic precursors, are strikingly diminished. These findings highlight a crucial and unexpected role for Sox2 in the maintenance of neurones in selected brain areas, and suggest a contribution of neural cell proliferative defects to the pathological phenotype.

Key words: Neural stem cells, Nervous system, Mouse, Sox2, Transcription factors, Neurogenesis, Hippocampal precursors, Neurodegeneration, Neuronal inclusions


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Stem CellsHome page
W. Ma, R.-T. Yan, X. Li, and S.-Z. Wang
Reprogramming Retinal Pigment Epithelium to Differentiate Toward Retinal Neurons with Sox2
Stem Cells, June 1, 2009; 27(6): 1376 - 1387.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
J. Que, X. Luo, R. J. Schwartz, and B. L. M. Hogan
Multiple roles for Sox2 in the developing and adult mouse trachea
Development, June 1, 2009; 136(11): 1899 - 1907.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
C. Gontan, T. Guttler, E. Engelen, J. Demmers, M. Fornerod, F. G. Grosveld, D. Tibboel, D. Gorlich, R. A. Poot, and R. J. Rottier
Exportin 4 mediates a novel nuclear import pathway for Sox family transcription factors
J. Cell Biol., April 6, 2009; 185(1): 27 - 34.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
K. S Alatzoglou, D. Kelberman, and M. T Dattani
The role of SOX proteins in normal pituitary development
J. Endocrinol., March 1, 2009; 200(3): 245 - 258.
[Abstract] [Full Text] [PDF]

Home page
 Cold Spring Harb Symp Quant BiolHome page
B.P. Levi and S.J. Morrison
Stem Cells Use Distinct Self-renewal Programs at Different Ages
Cold Spring Harb Symp Quant Biol, January 15, 2009; (2009) sqb.2008.73.049v1.
[Abstract] [PDF]

Home page
 IOVSHome page
Y.-p. Lin, Y. Ouchi, S. Satoh, and S. Watanabe
Sox2 Plays a Role in the Induction of Amacrine and Muller Glial Cells in Mouse Retinal Progenitor Cells
Invest. Ophthalmol. Vis. Sci., January 1, 2009; 50(1): 68 - 74.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
R. M. R. Gangemi, F. Griffero, D. Marubbi, M. Perera, M. C. Capra, P. Malatesta, G. L. Ravetti, G. L. Zona, A. Daga, and G. Corte
SOX2 Silencing in Glioblastoma Tumor-Initiating Cells Causes Stop of Proliferation and Loss of Tumorigenicity
Stem Cells, January 1, 2009; 27(1): 40 - 48.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
H. Takanaga, N. Tsuchida-Straeten, K. Nishide, A. Watanabe, H. Aburatani, and T. Kondo
Gli2 Is a Novel Regulator of Sox2 Expression in Telencephalic Neuroepithelial Cells
Stem Cells, January 1, 2009; 27(1): 165 - 174.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
D. Zou, C. Erickson, E.-H. Kim, D. Jin, B. Fritzsch, and P.-X. Xu
Eya1 gene dosage critically affects the development of sensory epithelia in the mammalian inner ear
Hum. Mol. Genet., November 1, 2008; 17(21): 3340 - 3356.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M. Alonso, I. Ortega-Perez, M. S. Grubb, J.-P. Bourgeois, P. Charneau, and P.-M. Lledo
Turning Astrocytes from the Rostral Migratory Stream into Neurons: A Role for the Olfactory Sensory Organ
J. Neurosci., October 22, 2008; 28(43): 11089 - 11102.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
C. Q. Doe
Neural stem cells: balancing self-renewal with differentiation
Development, May 1, 2008; 135(9): 1575 - 1587.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
R. D. Hodge, T. D. Kowalczyk, S. A. Wolf, J. M. Encinas, C. Rippey, G. Enikolopov, G. Kempermann, and R. F. Hevner
Intermediate Progenitors in Adult Hippocampal Neurogenesis: Tbr2 Expression and Coordinate Regulation of Neuronal Output
J. Neurosci., April 2, 2008; 28(14): 3707 - 3717.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
C. Freund, D. Ward-van Oostwaard, J. Monshouwer-Kloots, S. van den Brink, M. van Rooijen, X. Xu, R. Zweigerdt, C. Mummery, and R. Passier
Insulin Redirects Differentiation from Cardiogenic Mesoderm and Endoderm to Neuroectoderm in Differentiating Human Embryonic Stem Cells
Stem Cells, March 1, 2008; 26(3): 724 - 733.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Fauquier, K. Rizzoti, M. Dattani, R. Lovell-Badge, and I. C. A. F. Robinson
SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland
PNAS, February 26, 2008; 105(8): 2907 - 2912.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
M. Cavallaro, J. Mariani, C. Lancini, E. Latorre, R. Caccia, F. Gullo, M. Valotta, S. DeBiasi, L. Spinardi, A. Ronchi, et al.
Impaired generation of mature neurons by neural stem cells from hypomorphic Sox2 mutants
Development, February 1, 2008; 135(3): 541 - 557.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
J. Malaterre, T. Mantamadiotis, S. Dworkin, S. Lightowler, Q. Yang, M. I. Ransome, A. M. Turnley, N. R. Nichols, N. R. Emambokus, J. Frampton, et al.
c-Myb Is Required for Neural Progenitor Cell Proliferation and Maintenance of the Neural Stem Cell Niche in Adult Brain
Stem Cells, January 1, 2008; 26(1): 173 - 181.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
M. Zhao, S. A Amiel, M. R Christie, P. Muiesan, P. Srinivasan, W. Littlejohn, M. Rela, M. Arno, N. Heaton, and G. C. Huang
Evidence for the presence of stem cell-like progenitor cells in human adult pancreas
J. Endocrinol., December 1, 2007; 195(3): 407 - 414.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
R. S. Ashton, J. Peltier, C. A. Fasano, A. O'Neill, J. Leonard, S. Temple, D. V. Schaffer, and R. S. Kane
High-Throughput Screening of Gene Function in Stem Cells Using Clonal Microarrays
Stem Cells, November 1, 2007; 25(11): 2928 - 2935.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
M. Ferletta, L. Uhrbom, T. Olofsson, F. Ponten, and B. Westermark
Sox10 Has a Broad Expression Pattern in Gliomas and Enhances Platelet-Derived Growth Factor-B Induced Gliomagenesis
Mol. Cancer Res., September 1, 2007; 5(9): 891 - 897.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
I. Nakano, J. D. Dougherty, K. Kim, I. Klement, D. H. Geschwind, and H. I. Kornblum
Phosphoserine Phosphatase Is Expressed in the Neural Stem Cell Niche and Regulates Neural Stem and Progenitor Cell Proliferation
Stem Cells, August 1, 2007; 25(8): 1975 - 1984.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
J. M. Lawrence, S. Singhal, B. Bhatia, D. J. Keegan, T. A. Reh, P. J. Luthert, P. T. Khaw, and G. A. Limb
MIO-M1 Cells and Similar Muller Glial Cell Lines Derived from Adult Human Retina Exhibit Neural Stem Cell Characteristics
Stem Cells, August 1, 2007; 25(8): 2033 - 2043.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. V. Pfenninger, T. Roschupkina, F. Hertwig, D. Kottwitz, E. Englund, J. Bengzon, S. E. Jacobsen, and U. A. Nuber
CD133 Is Not Present on Neurogenic Astrocytes in the Adult Subventricular Zone, but on Embryonic Neural Stem Cells, Ependymal Cells, and Glioblastoma Cells
Cancer Res., June 15, 2007; 67(12): 5727 - 5736.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
P. Chapouton, B. Adolf, C. Leucht, B. Tannhauser, S. Ryu, W. Driever, and L. Bally-Cuif
her5 expression reveals a pool of neural stem cells in the adult zebrafish midbrain
Development, November 1, 2006; 133(21): 4293 - 4303.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Miyagi, M. Nishimoto, T. Saito, M. Ninomiya, K. Sawamoto, H. Okano, M. Muramatsu, H. Oguro, A. Iwama, and A. Okuda
The Sox2 Regulatory Region 2 Functions as a Neural Stem Cell-specific Enhancer in the Telencephalon
J. Biol. Chem., May 12, 2006; 281(19): 13374 - 13381.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
O. V. Taranova, S. T. Magness, B. M. Fagan, Y. Wu, N. Surzenko, S. R. Hutton, and L. H. Pevny
SOX2 is a dose-dependent regulator of retinal neural progenitor competence.
Genes & Dev., May 1, 2006; 20(9): 1187 - 1202.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
X. Shan, L. Chi, M. Bishop, C. Luo, L. Lien, Z. Zhang, and R. Liu
Enhanced De Novo Neurogenesis and Dopaminergic Neurogenesis in the Substantia Nigra of 1-Methyl-4-phyenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinson's Disease-Like Mice
Stem Cells, May 1, 2006; 24(5): 1280 - 1287.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. E. Wilson, K. Y. Yang, A. Kalousova, J. Lau, Y. Kosaka, F. C. Lynn, J. Wang, C. Mrejen, V. Episkopou, H. C. Clevers, et al.
The HMG Box Transcription Factor Sox4 Contributes to the Development of the Endocrine Pancreas
Diabetes, December 1, 2005; 54(12): 3402 - 3409.
[Abstract] [Full Text] [PDF]

Home page
 ASH ANNUAL MEETING ABSTRACTSHome page
E. Levantini, F. Bertolotti, F. Cerisoli, A. L. Ferri, E. Brescia, D. Galvagno, D. G. Tenen, S. Ottolenghi, S. K. Nicolis, and M. C. Magli
New Role of the Regulatory Gene SOX2 in Hematopoiesis.
Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 4195 - 4195.
[Abstract]

Home page
 J. Biol. Chem.Home page
R. Catena, C. Tiveron, A. Ronchi, S. Porta, A. Ferri, L. Tatangelo, M. Cavallaro, R. Favaro, S. Ottolenghi, R. Reinbold, et al.
Conserved POU Binding DNA Sites in the Sox2 Upstream Enhancer Regulate Gene Expression in Embryonic and Neural Stem Cells
J. Biol. Chem., October 1, 2004; 279(40): 41846 - 41857.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2004