title: Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory.
abstract: During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9(-/-) adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9(-/-) mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors.
  
  
  
  Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo These cellular defects were associated with severe deficits in spatial learning and memory.
authors.affiliation: Curriculum in Neurobiology.
authors.forename: Cortney C
authors.initials: CC
authors.lastname: Winkle
authors.affiliation: Department of Pharmacology.
authors.forename: Reid H J
authors.initials: RH
authors.lastname: Olsen
authors.affiliation: Curriculum in Neurobiology.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Carolina Institute for Developmental Disabilities.
authors.forename: Sheryl S
authors.initials: SS
authors.lastname: Moy
authors.affiliation: Department of Pharmacology, University of North Carolina Neuroscience Center, sgupton@email.unc.edu juansong@email.unc.edu.
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.affiliation: University of North Carolina Neuroscience Center, Department of Cell Biology and Physiology, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 sgupton@email.unc.edu juansong@email.unc.edu.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Gupton
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D018891:Dentate Gyrus / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology / Q000166:cytology / Q000254:growth & development*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D000075388:Netrin-1; D009474:Neurons / Q000502:physiology*; D012903:Smell / Q000235:genetics; D065853:Spatial Learning / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; C469337:Trim9 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: TRIM9; arborization; learning; memory; neurogenesis