title: Npas4 regulates Mdm2 and thus Dcx in experience-dependent dendritic spine development of newborn olfactory bulb interneurons.
abstract: Sensory experience regulates the development of various brain structures, including the cortex, hippocampus, and olfactory bulb (OB). Little is known about how sensory experience regulates the dendritic spine development of OB interneurons, such as granule cells (GCs), although it is well studied in mitral/tufted cells. Here, we identify a transcription factor, Npas4, which is expressed in OB GCs immediately after sensory input and is required for dendritic spine formation. Npas4 overexpression in OB GCs increases dendritic spine density, even under sensory deprivation, and rescues reduction of dendrite spine density in the Npas4 knockout OB. Furthermore, loss of Npas4 upregulates expression of the E3-ubiquitin ligase Mdm2, which ubiquitinates a microtubule-associated protein Dcx. This leads to reduction in the dendritic spine density of OB GCs. Together, these findings suggest that Npas4 regulates Mdm2 expression to ubiquitinate and degrade Dcx during dendritic spine development in newborn OB GCs after sensory experience.
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Sei-Ichi
authors.initials: S
authors.lastname: Yoshihara
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Nobushiro
authors.initials: N
authors.lastname: Nishimura
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Asahina
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kitsuki
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Furukawa-Hibi
authors.affiliation: Department of Neurophysiology, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirai
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan. Electronic address: atsuboi@naramed-u.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Tsuboi
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism* / Q000502:physiology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007395:Interneurons / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D012903:Smell; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D051736:Proto-Oncogene Proteins c-mdm2; C000714847:Dcx protein, mouse; C533005:Npas4 protein, mouse; C497207:Mdm2 protein, mouse