title: Morphological characterization of mammalian timeless in the mouse brain development.
abstract: Timeless was originally identified in Drosophila as an essential component of circadian cycle regulation. In mammals, the ortholog of Timeless (Tim) has also implicated in cell cycle control and embryonic development. In this study, we generated a specific antibody against Tim, and carried out expression and localization analyses of Tim during mouse brain development. In Western blotting, Tim was detected throughout the developmental stage. In immunohistochemical analyses, Tim was detected strongly in neurons in the ventricular zone/subventricular zone and moderately in cortical neurons during corticogenesis. In adult mouse brain, Tim was observed moderately in cortical neurons. Notably, Tim was enriched in the nucleus of cortical neurons from embryonic to early postnatal stages while it was distributed in the cytoplasm in the adult stage. Similar distribution change from nucleus to cytoplasm was observed in the hippocampal neurons between P0 and P30. In situ hybridization revealed that the tissue expression profile of Tim-mRNA was similar to that of the protein. In differentiated primary cultured mouse hippocampal neurons, Tim was detected in cell body, axon and dendrites. The obtained results suggest that Tim is expressed in neuronal tissues in a spatiotemporally regulated manner and involved in developmental stage-specific neuronal functions.
authors.affiliation: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Aichi 480-0392, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Inaguma
authors.affiliation: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Aichi 480-0392, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.affiliation: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Aichi 480-0392, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Iwamoto
authors.affiliation: Department of Pediatrics, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Pediatrics, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamagata
authors.affiliation: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Aichi 480-0392, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Tabata
authors.affiliation: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Aichi 480-0392, Japan. Electronic address: knagata@inst-hsc.jp.
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000818:Animals; D000906:Antibodies; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology / Q000378:metabolism*
chemical_list: D000906:Antibodies; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C509770:Timeless protein, mouse
keywords: Antibody; Cerebral cortex; Development; Timeless