Article abstract


Nature Neuroscience 12, 259 - 267 (2009)
Published online: 22 February 2009 | doi:10.1038/nn.2268

Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke

Marie Carlén1,7, Konstantinos Meletis1,7, Christian Göritz1, Vladimer Darsalia2,3, Emma Evergren4, Kenji Tanigaki5, Mario Amendola6, Fanie Barnabé-Heider1, Maggie S Y Yeung1, Luigi Naldini6, Tasuku Honjo5, Zaal Kokaia2,3, Oleg Shupliakov4, Robert M Cassidy1, Olle Lindvall2,3 & Jonas Frisén1


Neurons are continuously generated from stem cells in discrete regions in the adult mammalian brain. We found that ependymal cells lining the lateral ventricles were quiescent and did not contribute to adult neurogenesis under normal conditions in mice but instead gave rise to neuroblasts and astrocytes in response to stroke. Ependymal cell quiescence was actively maintained by canonical Notch signaling. Inhibition of this pathway in uninjured animals allowed ependymal cells to enter the cell cycle and produce olfactory bulb neurons, whereas forced Notch signaling was sufficient to block the ependymal cell response to stroke. Ependymal cells were depleted by stroke and failed to self-renew sufficiently to maintain their own population. Thus, although ependymal cells act as primary cells in the neural lineage to produce neurons and glial cells after stroke, they do not fulfill defining criteria for stem cells under these conditions and instead serve as a reservoir that is recruited by injury.

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  1. Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.
  2. Wallenberg Neuroscience Center, University Hospital, SE-221 84 Lund, Sweden.
  3. Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, University Hospital, SE-221 84 Lund, Sweden.
  4. Department of Neuroscience, Karolinska Institute, SE-171 77 Stockholm, Sweden.
  5. Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Konoecho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
  6. Telethon Institute for Gene Therapy, San Raffaele Institute, via Olgettina 58, 20132 Milan, Italy.
  7. Present address: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Correspondence to: Jonas Frisén1 e-mail: jonas.frisen@ki.se



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