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Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6

Hack, MA ; Sugimori, M ; Lundberg, Cecilia LU orcid ; Nakafuku, M and Gotz, M (2004) In Molecular and Cellular Neuroscience 25(4). p.664-678
Abstract
Neurosphere cultures are widely used to propagate multipotent CNS precursors, but their differentiation into neurons or oligodendrocytes is rather poor. To elucidate fate determination in this system, we examined the expression and function of candidate transcription factors in neurospheres derived from different CNS regions during development and adulthood. We observed prominent down-regulation of most transcription factors present in telencephalic precursors upon growth factor exposure in neurosphere cultures while Olig1 and Olig2 expression was strongly up-regulated. Interference with Olig2 in neurospheres revealed its role in self-renewal during expansion and for the generation of neurons and oligodendrocytes during differentiation. We... (More)
Neurosphere cultures are widely used to propagate multipotent CNS precursors, but their differentiation into neurons or oligodendrocytes is rather poor. To elucidate fate determination in this system, we examined the expression and function of candidate transcription factors in neurospheres derived from different CNS regions during development and adulthood. We observed prominent down-regulation of most transcription factors present in telencephalic precursors upon growth factor exposure in neurosphere cultures while Olig1 and Olig2 expression was strongly up-regulated. Interference with Olig2 in neurospheres revealed its role in self-renewal during expansion and for the generation of neurons and oligodendrocytes during differentiation. We further show that neurogenesis becomes fully Pax6-dependent in the neurosphere culture system, independent of the region of origin, and that Pax6 overexpression is sufficient to direct almost all neurosphere-derived cells towards neurogenesis. Thus, a pathway combining transcription factors of dorsal and ventral regions is activated in the neurosphere culture model. (C) 2004 Elsevier Inc. All rights reserved. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular and Cellular Neuroscience
volume
25
issue
4
pages
664 - 678
publisher
Elsevier
external identifiers
  • pmid:15080895
  • wos:000220852400011
  • scopus:1842689282
ISSN
1044-7431
DOI
10.1016/j.mcn.2003.12.012
language
English
LU publication?
yes
id
c1d94c22-7b68-42a6-afed-14202d29aaa4 (old id 281137)
date added to LUP
2016-04-01 12:29:16
date last changed
2022-03-21 05:00:18
@article{c1d94c22-7b68-42a6-afed-14202d29aaa4,
  abstract     = {{Neurosphere cultures are widely used to propagate multipotent CNS precursors, but their differentiation into neurons or oligodendrocytes is rather poor. To elucidate fate determination in this system, we examined the expression and function of candidate transcription factors in neurospheres derived from different CNS regions during development and adulthood. We observed prominent down-regulation of most transcription factors present in telencephalic precursors upon growth factor exposure in neurosphere cultures while Olig1 and Olig2 expression was strongly up-regulated. Interference with Olig2 in neurospheres revealed its role in self-renewal during expansion and for the generation of neurons and oligodendrocytes during differentiation. We further show that neurogenesis becomes fully Pax6-dependent in the neurosphere culture system, independent of the region of origin, and that Pax6 overexpression is sufficient to direct almost all neurosphere-derived cells towards neurogenesis. Thus, a pathway combining transcription factors of dorsal and ventral regions is activated in the neurosphere culture model. (C) 2004 Elsevier Inc. All rights reserved.}},
  author       = {{Hack, MA and Sugimori, M and Lundberg, Cecilia and Nakafuku, M and Gotz, M}},
  issn         = {{1044-7431}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{664--678}},
  publisher    = {{Elsevier}},
  series       = {{Molecular and Cellular Neuroscience}},
  title        = {{Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6}},
  url          = {{http://dx.doi.org/10.1016/j.mcn.2003.12.012}},
  doi          = {{10.1016/j.mcn.2003.12.012}},
  volume       = {{25}},
  year         = {{2004}},
}