Article abstract
Nature Neuroscience 11, 277 - 284 (2008)
Published online: 24 February 2008 | doi:10.1038/nn2059
Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells
Young-Goo Han1, Nathalie Spassky2, Miriam Romaguera-Ros3, Jose-Manuel Garcia-Verdugo3, Andrea Aguilar2, Sylvie Schneider-Maunoury4 & Arturo Alvarez-Buylla1
Abstract
Neural stem cells that continue to produce neurons are retained in the adult hippocampal dentate gyrus. The mechanisms by which embryonic neural progenitors expand and transform into postnatal neural stem cells, an essential process for the continual production of neurons throughout life, remain unknown. We found that radial astrocytes, the postnatal progenitors in the dentate gyrus, failed to develop after embryonic ablation of ciliary genes or Smoothened (Smo), an essential component for Sonic hedgehog (Shh) signaling. Postnatal dentate neurogenesis failed in these mutant mice, and the dentate gyrus became severely hypotrophic. In contrast, expression of a constitutively active Smo (SmoM2-YFP) resulted in a marked expansion of the dentate gyrus. Double-mutant analyses suggested that both wild-type Smo and SmoM2-YFP function through the primary cilia. We conclude that Shh signaling, acting through the primary cilia, has a critical role in the expansion and establishment of postnatal hippocampal progenitors.
- Department of Neurological Surgery, Institute for Regeneration Medicine, University of California San Francisco, San Francisco, California 94143, USA.
- Université Pierre and Marie Curie-Paris 6, IFR des Neurosciences, Hôpital Pitié-Salpêtrière, INSERM, U711, Paris, F-75013 France.
- Laboratorio de Morfologia Celular, Unidad asociada Universidad de Valencia and Centro de Investigacion Principe Felipe, Valencia, 46100 Spain.
- CNRS UMR7622, Université Pierre et Marie Curie, 9 Quai Saint Bernard, 75005 Paris, France.
Correspondence to: Arturo Alvarez-Buylla1 e-mail: abuylla@stemcell.ucsf.edu
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