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The Journal of Neuroscience, August 1, 2007, 27(31):8286-8296; doi:10.1523/JNEUROSCI.0476-07.2007

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Development/Plasticity/Repair
Subventricular Zone Stem Cells Are Heterogeneous with Respect to Their Embryonic Origins and Neurogenic Fates in the Adult Olfactory Bulb

Kaylene M. Young, Matthew Fogarty, Nicoletta Kessaris, ^* and William D. Richardson ^*

Wolfson Institute for Biomedical Research and Department of Biology, University College London, London WC1E 6BT, United Kingdom

Correspondence should be addressed to William D. Richardson, Wolfson Institute for Biomedical Research and Department of Biology, University College London, Gower Street, London WC1E 6BT, UK. Email: w.richardson{at}ucl.ac.uk

We determined the embryonic origins of adult forebrain subventricular zone (SVZ) stem cells by Cre-lox fate mapping in transgenic mice. We found that all parts of the telencephalic neuroepithelium, including the medial ganglionic eminence and lateral ganglionic eminence (LGE) and the cerebral cortex, contribute multipotent, self-renewing stem cells to the adult SVZ. Descendants of the embryonic LGE and cortex settle in ventral and dorsal aspects of the dorsolateral SVZ, respectively. Both populations contribute new (5-bromo-2'-deoxyuridine-labeled) tyrosine hydroxylase- and calretinin-positive interneurons to the adult olfactory bulb. However, calbindin-positive interneurons in the olfactory glomeruli were generated exclusively by LGE-derived stem cells. Thus, different SVZ stem cells have different embryonic origins, colonize different parts of the SVZ, and generate different neuronal progeny, suggesting that some aspects of embryonic patterning are preserved in the adult SVZ. This could have important implications for the design of endogenous stem cell-based therapies in the future.

Key words: adult; mouse; subventricular zone; neural stem cells; olfactory bulb; interneurons; Cre-lox fate mapping; Gsh2; Emx1

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Received Feb. 2, 2007; revised June 6, 2007; accepted June 7, 2007.

Correspondence should be addressed to William D. Richardson, Wolfson Institute for Biomedical Research and Department of Biology, University College London, Gower Street, London WC1E 6BT, UK. Email: w.richardson{at}ucl.ac.uk

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