title: Analysis of the expression and function of BRINP family genes during neuronal differentiation in mouse embryonic stem cell-derived neural stem cells.
abstract: We previously identified a novel family of genes, BRINP1, 2, and 3, that are predominantly and widely expressed in both the central nervous system (CNS) and peripheral nervous system (PNS). In the present study, we analyzed the expression pattern of three BRINP genes during differentiation of mouse embryonic stem (ES) cell-derived neural stem cells (NSCs) and their effects on the cell-cycle regulation of NSCs. While there was no significant expression of any BRINP-mRNA expressed in mouse ES cells, BRINP 1 and 2-mRNAs was expressed at high levels in the ES cell-derived neural stem cells. Upon differentiation into neuronal cells in the presence of retinoic acid and BDNF, all three types of BRINP-mRNA were induced with a similar time course peaking at day three of treatment. Upon differentiation into astroglial cells in the presence of serum, BRINP1-mRNA was slightly up-regulated, while BRINP2- and BRINP3-mRNAs were almost abolished in the astrocytes. While 69.2, 26.1, and 7.7% of cells in a population of NSCs in the exponentially growing phase were in the G1, S and G2 phases, respectively, over-expression of any one of the three BRINP genes completely abolished cells in the G2 phase and significantly reduced the cells in S phase to 11.8-13.8%. Based on these results, the physiological roles of induced BRINP genes in the cell-cycle suppression of terminally differentiated post-mitotic neurons are discussed.
authors.affiliation: Division of Innovative Research, Creative Research Initiative SOUSEI (CRIS), Hokkaido University, Sapporo, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Terashima
authors.forename: Miwako
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Motomiya
authors.forename: Nobuo
authors.initials: N
authors.lastname: Inoue
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Norimasa
authors.initials: N
authors.lastname: Iwasaki
authors.forename: Akio
authors.initials: A
authors.lastname: Minami
authors.forename: Ichiro
authors.initials: I
authors.lastname: Matsuoka
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D018816:Genes, cdc / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016196:S Phase / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology
chemical_list: C491992:BRINP1 protein, mouse; C491995:BRINP2 protein, rat; C491993:BRINP3 protein, rat; D019208:Brain-Derived Neurotrophic Factor; D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014212:Tretinoin