Persistent Sonic Hedgehog Signaling in Adult Brain Determines Neural Stem Cell Positional Identity
Open accessAbstract
Neural stem cells (NSCs) persist in the subventricular zone (SVZ) of the adult brain. Location within this germinal region determines the type of neuronal progeny NSCs generate, but the mechanism of adult NSC positional specification remains unknown. We show that sonic hedgehog (Shh) signaling, resulting in high gli1 levels, occurs in the ventral SVZ and is associated with the genesis of specific neuronal progeny. Shh is selectively produced by a small group of ventral forebrain neurons. Ablation of Shh decreases production of ventrally derived neuron types, while ectopic activation of this pathway in dorsal NSCs respecifies their progeny to deep granule interneurons and calbindin-positive periglomerular cells. These results show that Shh is necessary and sufficient for the specification of adult ventral NSCs.
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Active Shh signaling is present in the adult brain.
“More recent reports identified active Shh signaling in the adult brain [27–29].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [27]
The Sonic hedgehog (Shh) signaling pathway plays a pivotal role in development and neurogenesis.
“The Sonic hedgehog (Shh) signaling pathway is best known for its pivotal role in development and neurogenesis [23–28].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [27]
Wnt and Smoothened signaling, as well as primary cilium pathways, were up-regulated in male lateral and female septal samples.
“Wnt and Smoothened signaling, as well as primary cilium pathways (Ahn and Joyner, 2005; Azim et al., 2014; Ihrie et al., 2011), were up-regulated in male lateral and female septal samples.”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Ihrie et al., 2011
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- Authors
- Ihrie, R. A., Shah, J. K., Harwell, C. C., Levine, J. H., Guinto, C. D., Lezameta, M., Kriegstein, A. R., & Alvarez-Buylla, A.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 71
- Issue
- 2
- Pages
- 250-262
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3346180
- OpenAlex
- W2005455824
- Cited by
- 255
- References
- 68
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 8 · 2023: 13 · 2022: 16 · 2021: 11 · 2020: 16 · 2019: 19 · 2018: 17 · 2017: 16 · 2016: 26 · 2015: 22 · 2014: 32 · 2013: 25 · 2012: 17
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R37NS028478, NS-28478, R01NS028478)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD32116, R37HD032116, R01HD032116)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Sonic hedgehog signaling, neural stem cells, subventricular zone, positional identity, Gli1, periglomerular cells, adult neurogenesis
- MeSH terms
- Zinc Finger Protein GLI1, Smoothened Receptor, Age Factors, Animals, Cell Movement, Cerebral Ventricles, Choline O-Acetyltransferase, Cytarabine, Estrogen Antagonists, Gene Expression Regulation, Immunosuppressive Agents, Luminescent Proteins, Mice, Transgenic, Neurons, Olfactory Bulb, RNA, Messenger, Stilbamidines, Tamoxifen, Time Factors, Tyrosine 3-Monooxygenase, Signal Transduction, Receptors, G-Protein-Coupled, Mice, Kruppel-Like Transcription Factors, Hedgehog Proteins, Neural Stem Cells, Calbindins, S100 Calcium Binding Protein G
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