title: The transcriptional repressor RP58 is crucial for cell-division patterning and neuronal survival in the developing cortex.
abstract: The neocortex and the hippocampus comprise several specific layers containing distinct neurons that originate from progenitors at specific development times, under the control of an adequate cell-division patterning mechanism. Although many molecules are known to regulate this cell-division patterning process, its details are not well understood. Here, we show that, in the developing cerebral cortex, the RP58 transcription repressor protein was expressed both in postmitotic glutamatergic projection neurons and in their progenitor cells, but not in GABAergic interneurons. Targeted deletion of the RP58 gene led to dysplasia of the neocortex and of the hippocampus, reduction of the number of mature cortical neurons, and defects of laminar organization, which reflect abnormal neuronal migration within the cortical plate. We demonstrate an impairment of the cell-division patterning during the late embryonic stage and an enhancement of apoptosis of the postmitotic neurons in the RP58-deficient cortex. These results suggest that RP58 controls cell division of progenitor cells and regulates the survival of postmitotic cortical neurons.
authors.affiliation: Department of Molecular Physiology, Tokyo Metropolitan Institute for Neuroscience, Musashidai, Fuchu, Japan. hokado@tmin.ac.jp
authors.forename: Haruo
authors.initials: H
authors.lastname: Okado
authors.forename: Chiaki
authors.initials: C
authors.lastname: Ohtaka-Maruyama
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Sugitani
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Reiko
authors.initials: R
authors.lastname: Ishida
authors.forename: Shinobu
authors.initials: S
authors.lastname: Hirai
authors.forename: Akiko
authors.initials: A
authors.lastname: Miwa
authors.forename: Akiyo
authors.initials: A
authors.lastname: Takahashi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Aoki
authors.forename: Keiji
authors.initials: K
authors.lastname: Mochida
authors.forename: Osamu
authors.initials: O
authors.lastname: Suzuki
authors.forename: Takao
authors.initials: T
authors.lastname: Honda
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakajima
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ogawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Terashima
authors.forename: Junichiro
authors.initials: J
authors.lastname: Matsuda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kawano
authors.forename: Masataka
authors.initials: M
authors.lastname: Kasai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D012097:Repressor Proteins; C520669:Zbtb18 protein, mouse