title: Brd2 is required for cell cycle exit and neuronal differentiation through the E2F1 pathway in mouse neuroepithelial cells.
abstract: To understand genetic programs controlling mammalian central nervous system (CNS) development, we have identified one transgene-inserted mutation, which showed embryonic lethality during neurulation. Determination of the transgene integration site and rescue experiments revealed that the Brd2 gene, whose products specifically bind acetylated histone H4 and can mediate transcription, was the cause of this mutation. Expression studies with specific markers demonstrated that cell cycle progression was accelerated and neuronal differentiation as well as cell cycle exit were impaired in Brd2-deficient neruoepithelial cells. To investigate whether Brd2 regulates neuronal differentiation through a E2F1 transcriptional factor, which directly binds Brd2 and controls genes expression for cell cycle progression and exit, we analyzed Brd2;E2F1 double mutant phenotypes and, consequently found that abnormalities in neuronal differentiation and cell cycle progression due to Brd2-deficiency were restored by removing the E2F1 gene. These findings suggest that Brd2 is required for cell cycle exit and neuronal differentiation of neuroepithelial cells through the E2F1 pathway during mouse CNS development.
authors.affiliation: Department of Molecular Embryology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, Izumi, Osaka 594-1101, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Tsume
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kimura-Yoshida
authors.forename: Kyoko
authors.initials: K
authors.lastname: Mochida
authors.forename: Yukinao
authors.initials: Y
authors.lastname: Shibukawa
authors.forename: Saori
authors.initials: S
authors.lastname: Amazaki
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Wada
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hiramatsu
authors.forename: Kayo
authors.initials: K
authors.lastname: Shimokawa
authors.forename: Isao
authors.initials: I
authors.lastname: Matsuo
mesh_terms: D000483:Alleles; D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002490:Central Nervous System / Q000254:growth & development* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D046569:Neuroepithelial Cells / Q000166:cytology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D050687:E2F1 Transcription Factor; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; C490844:Brd2 protein, mouse; D000092468:Bromodomain Containing Proteins; C493754:E2f1 protein, mouse