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1 Department of Anatomy and Cell Biology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
2 Ottawa Health Research Institute, Ottawa Hospital and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1Y 4E9, Canada
* These authors contributed equally to this work
Present address: Department of Neurology, University of Tokyo, Tokyo 113-8655, Japan
Present address: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Author for correspondence (e-mail: derek.van.der.kooy{at}utoronto.ca)
Accepted 2 October 2001
Regional patterning in the developing mammalian brain is partially regulated by restricted gene expression patterns within the germinal zone, which is composed of stem cells and their progenitor cell progeny. Whether or not neural stem cells, which are considered at the top of the neural lineage hierarchy, are regionally specified remains unknown. Here we show that the cardinal properties of neural stem cells (self-renewal and multipotentiality) are conserved among embryonic cortex, ganglionic eminence and midbrain/hindbrain, but that these different stem cells express separate molecular markers of regional identity in vitro, even after passaging. Neural stem cell progeny derived from ganglionic eminence but not from other regions are specified to respond to local environmental cues to migrate ventrolaterally, when initially deposited on the germinal layer of ganglionic eminence in organotypic slice cultures. Cues exclusively from the ventral forebrain in a 5 day co-culture paradigm could induce both early onset and late onset marker gene expression of regional identity in neural stem cell colonies derived from both the dorsal and ventral forebrain as well as from the midbrain/hindbrain. Thus, neural stem cells and their progeny are regionally specified in the developing brain, but this regional identity can be altered by local inductive cues.
Key words: Emx1, Dlx2, En1, Dlx5, Neurosphere, Mouse, Cell fate
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