title: Persistent sonic hedgehog signaling in adult brain determines neural stem cell positional identity.
abstract: 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.
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Ihrie
authors.forename: Jugal K
authors.initials: JK
authors.lastname: Shah
authors.forename: Corey C
authors.initials: CC
authors.lastname: Harwell
authors.forename: Jacob H
authors.initials: JH
authors.lastname: Levine
authors.forename: Cristina D
authors.initials: CD
authors.lastname: Guinto
authors.forename: Melissa
authors.initials: M
authors.lastname: Lezameta
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Kriegstein
authors.forename: Arturo
authors.initials: A
authors.lastname: Alvarez-Buylla
mesh_terms: D000367:Age Factors; D000818:Animals; D064026:Calbindins; D002465:Cell Movement / Q000502:physiology*; D002552:Cerebral Ventricles / Q000166:cytology* / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003561:Cytarabine / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000072086:Smoothened Receptor; D013266:Stilbamidines; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D064026:Calbindins; D004965:Estrogen Antagonists; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D007166:Immunosuppressive Agents; D051741:Kruppel-Like Transcription Factors; D008164:Luminescent Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D064030:S100 Calcium Binding Protein G; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D013266:Stilbamidines; D000071676:Zinc Finger Protein GLI1; D003561:Cytarabine; D013629:Tamoxifen; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase