title: Primary cilia are required in a unique subpopulation of neural progenitors.
abstract: The apical domain of embryonic (radial glia) and adult (B1 cells) neural stem cells (NSCs) contains a primary cilium. This organelle has been suggested to function as an antenna for the detection of morphogens or growth factors. In particular, primary cilia are essential for Hedgehog (Hh) signaling, which plays key roles in brain development. Their unique location facing the ventricular lumen suggests that primary cilia in NSCs could play an important role in reception of signals within the cerebrospinal fluid. Surprisingly, ablation of primary cilia using conditional alleles for genes essential for intraflagellar transport [kinesin family member 3A (Kif3a) and intraflagellar transport 88 (Ift88)] and Cre drivers that are activated at early [Nestin; embryonic day 10.5 (E10.5)] and late [human glial fibrillary acidic protein (hGFAP); E13.5] stages of mouse neural development resulted in no apparent developmental defects. Neurogenesis in the ventricular-subventricular zone (V-SVZ) shortly after birth was also largely unaffected, except for a restricted ventral domain previously known to be regulated by Hh signaling. However, Kif3a and Ift88 genetic ablation also disrupts ependymal cilia, resulting in hydrocephalus by postnatal day 4. To directly study the role of B1 cells' primary cilia without the confounding effects of hydrocephalus, we stereotaxically targeted elimination of Kif3a from a subpopulation of radial glia, which resulted in ablation of primary cilia in a subset of B1 cells. Again, this experiment resulted in decreased neurogenesis only in the ventral V-SVZ. Primary cilia ablation led to disruption of Hh signaling in this subdomain. We conclude that primary cilia are required in a specific Hh-regulated subregion of the postnatal V-SVZ.
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143; Neuroscience Graduate Program, University of California, San Francisco, CA 94158; and.
authors.forename: Cheuk Ka
authors.initials: CK
authors.lastname: Tong
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: Young-Goo
authors.initials: YG
authors.lastname: Han
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143;
authors.forename: Jugal K
authors.initials: JK
authors.lastname: Shah
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143;
authors.forename: Kirsten
authors.initials: K
authors.lastname: Obernier
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143;
authors.forename: Cristina D
authors.initials: CD
authors.lastname: Guinto
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143; Neuroscience Graduate Program, University of California, San Francisco, CA 94158; and abuylla@stemcell.ucsf.edu.
authors.forename: Arturo
authors.initials: A
authors.lastname: Alvarez-Buylla
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D049109:Cell Proliferation; D002923:Cilia / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000145:classification / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D055785:Gene Knockdown Techniques; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000145:classification* / Q000378:metabolism / Q000648:ultrastructure*; D055495:Neurogenesis / Q000502:physiology; D011247:Pregnancy; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D053823:Hedgehog Proteins; C490202:Kif3a protein, mouse; C577485:Nes protein, mouse; D064231:Nestin; C490898:Tg737Rpw protein, mouse; D025521:Tumor Suppressor Proteins; D016547:Kinesins
keywords: Gli1; adult neurogenesis; olfactory bulb; subependyma; ventricular zone
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