title: Cell cycle regulation in mouse heart during embryonic and postnatal stages.
abstract: The regulation of cardiomyocyte proliferation is important for heart development and function. Proliferation levels of mouse cardiomyocytes are high during early embryogenesis and start to decrease at midgestation. Many cardiomyocytes undergo mitosis without cytokinesis, resulting in binucleated cardiomyocytes during early postnatal stages, following which the cell cycle arrests irreversibly. It remains unknown how the proliferation pattern is regulated, and how the irreversible cell cycle arrest occurs. To clarify the mechanisms, fundamental information about cell cycle regulators in cardiomyocytes and cell cycle patterns during embryonic and postnatal stages is necessary. Here, we show that the expression, complex formation, and activity of main cyclins and cyclin-dependent kinases (CDKs) changed in a synchronous manner during embryonic and postnatal stages. These levels decreased from midgestation to birth, and then showed one wave in which the peak was around postnatal day 5. Detailed analysis of the complexes suggested that CDK activities were inhibited before the protein levels decreased. Analysis of DNA content distribution patterns in mono- and binucleated cardiomyocytes after birth revealed changes in cell cycle distribution patterns and the transition from mono- to binucleated cells. These analyses indicated that the wave of cell cycle regulator expression or activities during postnatal stages mainly produced binucleated cells from mononucleated cells. The data obtained should provide a basis for the analysis of cell cycle regulation in cardiomyocytes during embryonic and postnatal stages.
authors.affiliation: School of Life Sciences, Faculty of Medicine, Tottori University, Yonago, 683-8503, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Ikenishi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Okayama
authors.forename: Noriko
authors.initials: N
authors.lastname: Iwamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshitome
authors.forename: Shoji
authors.initials: S
authors.lastname: Tane
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Obayashi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D048749:Cytokinesis; D006321:Heart / Q000196:embryology* / Q000254:growth & development*; D051379:Mice; D008809:Mice, Inbred C3H; D008938:Mitosis; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D016213:Cyclins; D018844:Cyclin-Dependent Kinases