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Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin Coremans, Vanessa; Ahmed, Tariq; Balschun, Detlef; D'Hooge, Rudi; DeVriese, Astrid; Cremer, Jonathan; Antonucci, Flavia; Moons, Michaël; Baekelandt, Veerle; Reumers, Veerle; Cremer, Harold; Eisch, Amelia; Lagace, Diane; Janssens, Tom; Bozzi, Yuri; Caleo, Matteo; Conway, Edward M.

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 (Survivin Camcre) 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. Survivin Camcrebrains 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.

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Title
Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin
Creator
Coremans, Vanessa; Ahmed, Tariq; Balschun, Detlef; D'Hooge, Rudi; DeVriese, Astrid; Cremer, Jonathan; Antonucci, Flavia; Moons, Michaël; Baekelandt, Veerle; Reumers, Veerle; Cremer, Harold; Eisch, Amelia; Lagace, Diane; Janssens, Tom; Bozzi, Yuri; Caleo, Matteo; Conway, Edward M.
Publisher
BioMed Central
Date Issued
2010-01-05
Description
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 (Survivin Camcre) 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. Survivin Camcrebrains 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.
Genre
Article
Type
Text
Language
eng
Date Available
2015-08-13
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0074599
URI
http://hdl.handle.net/2429/54400
Affiliation
Medicine, Faculty of; Non UBC
Citation
BMC Neuroscience. 2010 Jan 05;11(1):2
Publisher DOI
10.1186/1471-2202-11-2
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
Coremans et al.
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)