title: Pten deletion in adult hippocampal neural stem/progenitor cells causes cellular abnormalities and alters neurogenesis.
abstract: Adult neurogenesis persists throughout life in restricted brain regions in mammals and is affected by various physiological and pathological conditions. The tumor suppressor gene Pten is involved in adult neurogenesis and is mutated in a subset of autism patients with macrocephaly; however, the link between the role of PTEN in adult neurogenesis and the etiology of autism has not been studied before. Moreover, the role of hippocampus, one of the brain regions where adult neurogenesis occurs, in development of autism is not clear. Here, we show that ablating Pten in adult neural stem cells in the subgranular zone of hippocampal dentate gyrus results in higher proliferation rate and accelerated differentiation of the stem/progenitor cells, leading to depletion of the neural stem cell pool and increased differentiation toward the astrocytic lineage at later stages. Pten-deleted stem/progenitor cells develop into hypertrophied neurons with abnormal polarity. Additionally, Pten mutant mice have macrocephaly and exhibit impairment in social interactions and seizure activity. Our data reveal a novel function for PTEN in adult hippocampal neurogenesis and indicate a role in the pathogenesis of abnormal social behaviors.
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA.
authors.forename: Anahita
authors.initials: A
authors.lastname: Amiri
authors.forename: Woosung
authors.initials: W
authors.lastname: Cho
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Shari G
authors.initials: SG
authors.lastname: Birnbaum
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Sinton
authors.forename: Renée M
authors.initials: RM
authors.lastname: McKay
authors.forename: Luis F
authors.initials: LF
authors.lastname: Parada
mesh_terms: D000221:Adaptation, Ocular / Q000235:genetics; D053687:Adult Stem Cells / Q000187:drug effects / Q000502:physiology*; D000367:Age Factors; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004576:Electromyography; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000235:genetics; D007398:Interpersonal Relations; D020547:Lateral Ventricles / Q000166:cytology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000172:deficiency*; D011412:Propanolamines / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D007381:Intermediate Filament Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D011412:Propanolamines; C025707:PS-6; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D001973:Bromodeoxyuridine