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 2 January 2008
doi: 10.1242/dev.010801

Development 135, 541-557 (2008)
Published by The Company of Biologists 2008
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
dev.010801v1
135/3/541    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 Cavallaro, M.
Right arrow Articles by Nicolis, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cavallaro, 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?

Impaired generation of mature neurons by neural stem cells from hypomorphic Sox2 mutants

Maurizio Cavallaro1,*, Jessica Mariani1,*, Cesare Lancini1,*, Elisa Latorre1, Roberta Caccia1, Francesca Gullo1, Menella Valotta1, Silvia DeBiasi2, Laura Spinardi1,3, Antonella Ronchi1, Enzo Wanke1, Silvia Brunelli4,5, Rebecca Favaro1, Sergio Ottolenghi1 and Silvia K. Nicolis1,{dagger}

1 Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
2 Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
3 Direzione Scientifica Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via Francesco Sforza 28, 20122 Milano, Italy.
4 Dipartimento di Medicina Sperimentale, Facoltà di Medicina, Università degli Studi di Milano-Bicocca, Via Cadore 48, 20052 Monza, Italy.
5 Stem Cell Research Institute, DIBIT H San Raffaele, Via Olgettina 58, 20132 Milano, Italy.

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

Accepted 5 November 2007

The transcription factor Sox2 is active in neural stem cells, and Sox2 `knockdown' mice show defects in neural stem/progenitor cells in the hippocampus and eye, and possibly some neurons. In humans, heterozygous Sox2 deficiency is associated with eye abnormalities, hippocampal malformation and epilepsy. To better understand the role of Sox2, we performed in vitro differentiation studies on neural stem cells cultured from embryonic and adult brains of `knockdown' mutants. Sox2 expression is high in undifferentiated cells, and declines with differentiation, but remains visible in at least some of the mature neurons. In mutant cells, neuronal, but not astroglial, differentiation was profoundly affected. β-Tubulin-positive cells were abundant, but most failed to progress to more mature neurons, and showed morphological abnormalities. Overexpression of Sox2 in neural cells at early, but not late, stages of differentiation, rescued the neuronal maturation defect. In addition, it suppressed GFAP expression in glial cells. Our results show an in vitro requirement for Sox2 in early differentiating neuronal lineage cells, for maturation and for suppression of alternative lineage markers. Finally, we examined newly generated neurons from Sox2 `knockdown' newborn and adult mice. GABAergic neurons were greatly diminished in number in newborn mouse cortex and in the adult olfactory bulb, and some showed abnormal morphology and migration properties. GABA deficiency represents a plausible explanation for the epilepsy observed in some of the knockdown mice, as well as in SOX2-deficient individuals.

Key words: Sox2, Neural stem cells, Neurogenesis, Transcription factors


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
 RNAHome page
P. P. Amaral, C. Neyt, S. J. Wilkins, M. E. Askarian-Amiri, S. M. Sunkin, A. C. Perkins, and J. S. Mattick
Complex architecture and regulated expression of the Sox2ot locus during vertebrate development
RNA, November 1, 2009; 15(11): 2013 - 2027.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
Y. Ishii, K. Weinberg, I. Oda-Ishii, L. Coughlin, and T. Mikawa
Morphogenesis and cytodifferentiation of the avian retinal pigmented epithelium require downregulation of Group B1 Sox genes
Development, August 1, 2009; 136(15): 2579 - 2589.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
B. W. Okaty, M. N. Miller, K. Sugino, C. M. Hempel, and S. B. Nelson
Transcriptional and Electrophysiological Maturation of Neocortical Fast-Spiking GABAergic Interneurons
J. Neurosci., May 27, 2009; 29(21): 7040 - 7052.
[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
 J. Cell Sci.Home 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
J. Cell Sci., February 1, 2008; 121(3): e307 - e307.
[Full Text]


© The Company of Biologists Ltd 2008