title: Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin.
abstract: BACKGROUND
  Survivin is a unique member of the inhibitor of apoptosis protein (IAP) family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated.
  
  
  RESULTS
  To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ) and the subgranular zone (SGZ). We then used a conditional gene inactivation strategy to delete the survivin gene prenatally in those neurogenic regions. Lack of embryonic NPC survivin results in viable, fertile mice (SurvivinCamcre) with reduced numbers of SVZ NPCs, absent rostral migratory stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as intracerebroventricular gene delivery of survivin during embryonic development increases olfactory bulb neurogenesis, detected postnatally. SurvivinCamcre brains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning.
  
  
  CONCLUSIONS
  The findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.
authors.affiliation: KU Leuven, VIB Vesalius Research Center, Herestraat 49, Gasthuisberg O&N1, B3000 Leuven, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Coremans
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmed
authors.forename: Detlef
authors.initials: D
authors.lastname: Balschun
authors.forename: Rudi
authors.initials: R
authors.lastname: D'Hooge
authors.forename: Astrid
authors.initials: A
authors.lastname: DeVriese
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cremer
authors.forename: Flavia
authors.initials: F
authors.lastname: Antonucci
authors.forename: Michaël
authors.initials: M
authors.lastname: Moons
authors.forename: Veerle
authors.initials: V
authors.lastname: Baekelandt
authors.forename: Veerle
authors.initials: V
authors.lastname: Reumers
authors.forename: Harold
authors.initials: H
authors.lastname: Cremer
authors.forename: Amelia
authors.initials: A
authors.lastname: Eisch
authors.forename: Diane
authors.initials: D
authors.lastname: Lagace
authors.forename: Tom
authors.initials: T
authors.lastname: Janssens
authors.forename: Yuri
authors.initials: Y
authors.lastname: Bozzi
authors.forename: Matteo
authors.initials: M
authors.lastname: Caleo
authors.forename: Edward M
authors.initials: EM
authors.lastname: Conway
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D003072:Cognition Disorders / Q000473:pathology / Q000503:physiopathology*; D020868:Gene Silencing; D051034:Inhibitor of Apoptosis Proteins; D007395:Interneurons / Q000473:pathology / Q000502:physiology; D007859:Learning Disabilities / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008569:Memory Disorders / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins; D012640:Seizures / Q000473:pathology / Q000503:physiopathology*; D055153:Stem Cell Niche / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D013234:Stem Cells / Q000473:pathology / Q000502:physiology*; D000077022:Survivin
chemical_list: C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D000077022:Survivin