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PMID:18297065

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Citation

Han, YG, Spassky, N, Romaguera-Ros, M, Garcia-Verdugo, JM, Aguilar, A, Schneider-Maunoury, S and Alvarez-Buylla, A (2008) Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat. Neurosci. 11:277-84

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.

Links

PubMed Online version:10.1038/nn2059

Keywords

Aging/genetics; Aging/metabolism; Animals; Astrocytes/cytology; Astrocytes/metabolism; Cell Differentiation/genetics; Cell Proliferation; Cells, Cultured; Cilia/metabolism; Cilia/ultrastructure; Dentate Gyrus/cytology; Dentate Gyrus/embryology; Dentate Gyrus/growth & development; Hedgehog Proteins/genetics; Hedgehog Proteins/metabolism; Hippocampus/cytology; Hippocampus/embryology; Hippocampus/growth & development; Kinesin/genetics; Kinesin/metabolism; Mice; Mice, Knockout; Mice, Neurologic Mutants; Receptors, G-Protein-Coupled/genetics; Receptors, G-Protein-Coupled/metabolism; Signal Transduction/genetics; Stem Cells/metabolism; Stem Cells/ultrastructure

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:KIF3A

acts_upstream_of_or_within

GO:0021542: dentate gyrus development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179048,MGI:MGI:2386464

P

  • occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:0007224: smoothened signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179048,MGI:MGI:2386464

P

  • occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:0061351: neural precursor cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179048,MGI:MGI:2386464

P

  • occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179048,MGI:MGI:2386464

P

  • occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

MOUSE:SMO

acts_upstream_of_or_within

GO:0021542: dentate gyrus development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176256,MGI:MGI:2179048

P

  • occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0061351: neural precursor cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2157527

P

  • occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

MOUSE:RPGR1

acts_upstream_of_or_within

GO:0061351: neural precursor cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3716208

P

Seeded From UniProt

complete

MOUSE:SMO

acts_upstream_of_or_within

GO:0021542: dentate gyrus development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176256,MGI:MGI:2179048

P

occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179048,MGI:MGI:2386464

P

occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:0061351: neural precursor cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179048,MGI:MGI:2386464

P

occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:0007224: smoothened signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179048,MGI:MGI:2386464

P

occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

MOUSE:KIF3A

acts_upstream_of_or_within

GO:0021542: dentate gyrus development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179048,MGI:MGI:2386464

P

occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

MOUSE:IFT88

acts_upstream_of_or_within

GO:0061351: neural precursor cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2157527

P

occurs_in:(EMAPA:19037)

Seeded From UniProt

complete

Notes

See also

References

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