Persistent sonic hedgehog signaling in adult brain determines neural stem cell positional identity.

Ihrie RA, Shah JK, Harwell CC, Levine JH, Guinto CD, Lezameta M, Kriegstein AR, Alvarez-Buylla A
Neuron. 2011 71 (2): 250-62

PMID: 21791285 · PMCID: PMC3346180 · DOI:10.1016/j.neuron.2011.05.018

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

MeSH Terms (28)

Age Factors Animals Calbindins Cell Movement Cerebral Ventricles Choline O-Acetyltransferase Cytarabine Estrogen Antagonists Gene Expression Regulation Hedgehog Proteins Immunosuppressive Agents Kruppel-Like Transcription Factors Luminescent Proteins Mice Mice, Transgenic Neural Stem Cells Neurons Olfactory Bulb Receptors, G-Protein-Coupled RNA, Messenger S100 Calcium Binding Protein G Signal Transduction Smoothened Receptor Stilbamidines Tamoxifen Time Factors Tyrosine 3-Monooxygenase Zinc Finger Protein GLI1

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