TY - JOUR
T1 - Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin
AU - Coremans, Vanessa
AU - Ahmed, Tariq
AU - Balschun, Detlef
AU - D'Hooge, Rudi
AU - DeVriese, Astrid
AU - Cremer, Jonathan
AU - Antonucci, Flavia
AU - Moons, Michaël
AU - Baekelandt, Veerle
AU - Reumers, Veerle
AU - Cremer, Harold
AU - Eisch, Amelia
AU - Lagace, Diane
AU - Janssens, Tom
AU - Bozzi, Yuri
AU - Caleo, Matteo
AU - Conway, Edward M.
N1 - Funding Information:
This work was supported in part by the Fonds voor Wetenschappelijk Onderzoek (FWO), Belgium. YB was supported by grants from Parents Against Childhood Epilepsy (PACE, Inc.), NY, USA, and the Italian National Research Council (CNR - “Ricerche Spontanee a Tema Libero” - RSTL Program).
PY - 2010/1/5
Y1 - 2010/1/5
N2 - 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.
AB - 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.
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U2 - 10.1186/1471-2202-11-2
DO - 10.1186/1471-2202-11-2
M3 - Article
C2 - 20051123
AN - SCOPUS:76749087506
SN - 1471-2202
VL - 11
JO - BMC Neuroscience
JF - BMC Neuroscience
M1 - 2
ER -