Papers - Takahashi, Takao

The G1 restriction point as critical regulator of neocortical neuronogenesis.

'Caviness Verne S Jr, Takahashi Takao, Nowakowski Richard S'

Neurochemical Research 24 ( 4 ) 497-506 1999.04

Research paper (scientific journal), Joint Work

うっ血乳頭で発見された上矢状静脈洞血栓症の2症例

'Kaburaki Akiko, Mashima Yukihiko, Ando Yasutaka, Oguchi Yoshihisa, Takahashi Takao'

神経眼科 15 ( 3 ) 318-324 1998.09

Research paper (scientific journal), Joint Work

La cytogenese neocorticale: le gradient proliferatif de l'epithelium pseudostratifie ventriculaire(PVE) et histogenese du cortex cerebral

'Caviness Verne S Jr, Takahashi Takao'

Percentiel 3   5月10日 1998

Research paper (scientific journal), Joint Work

A gradient in the duration of the G1 phase in the murine neocortical proliferative epithelium

'Miyama S, Takahashi T, Nowakowski RS, Caviness VS Jr.'

Cereb Cortex 7   678-689 1997.10

Research paper (scientific journal), Joint Work

Mathematics of neocortical neruonogenesis

'Takahashi Takao, Nowakowski RS, Caviness VS Jr'

Exp Neurosci 19   17-22 1997.02

Research paper (scientific journal), Joint Work

The leaving or Q fraction of the murine cerebral PVE and a generalmodel of neocortical neuronogenesis

'Takahashi Takao, Nowakowski RS, Caviness VS Jr'

J Neurosci 16   6183-6196 1996.10

Research paper (scientific journal), Joint Work

Interkinetic and migratory behavior of a cohort of neocortical neurons arising in the early embryonic murine cerebral wall

'Takahashi Takao, Nowakowski RS, Caviness VS Jr'

J Neurosci 16   5762-5776 1996.09

Research paper (scientific journal), Joint Work

Number of specific antibody-secreting cells in the peripheral blood among children with Mycoplasma pneumonia

'Iseki Mikiro, Takahashi Takao, Kimura Kyoko, Yamashita Ryoko, Sasaki Tsuguo'

Infect Immun 64 ( 7 ) 2799-2803 1996.07

Research paper (scientific journal), Joint Work

Regulation of normal proliferation in the developing cerebrum:Potentital actions of trophic factors

'Caviness VS Jr, Takahashi Takao, Miyama Sahoko, Nowakowski RS, Ivana Delalle Nowakowski RS, Caviness VS Jr'

Exp Neuro 137   357-366 1996.04

Research paper (scientific journal), Joint Work

'Numbers, time and neocortical neuronogenesis ・ A general developmental and evolutionary model'

'Caviness VS Jr, Takahashi T, Nowakowski RS'

Trends Neurosci 18 ( 9 ) 379-383 1995.12

Research paper (scientific journal), Joint Work

Early ontogeny of the secondary proliferative population of the embryonic murine cerebral wall

'Takahashi T, Nowakowski RS, Caviness Jr VS'

J Neurosci 15 ( 9 ) 6058-6068 1995.09

Research paper (scientific journal), Joint Work

The cell cycle of the pseudostratified ventricular epithelium of the murine cerebral wall

'Takahashi T, Nowakowski RS, Caviness Jr VS'

J Neurosci 15 ( 9 ) 6046-6057 1995.09

Research paper (scientific journal), Joint Work

Proliferative events in the cerebral ventricular zone

'Caviness VS Jr, Takahashi T'

Brain & Development 17 ( 3 ) 159-163 1995.06

Research paper (scientific journal), Joint Work

Mode of cell proliferation in the developing mouse neocortex

T. Takahashi, R. S. Nowakowski and V. S. Caviness, Jr.

Proc Natl Acad Sci, USA 91 ( 1 ) 375 - 9 1994.01

ISSN  0027-8424

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There are two proliferative populations in the developing cerebral wall: the pseudostratified ventricular epithelium (PVE) and the secondary proliferative population (SPP). The present experiments provide on embryonic day 14 (E14) in the mouse direct measures of the values for the proportions of daughter cells that continue to proliferate (proliferative, P fraction, or P) and for those that leave the cell cycle (quiescent, Q fraction, or Q; Q = 1 - P) for both of these populations. The range of values of P for the PVE, 0.62-0.66, would provide for the relatively low rate of neuronal output and for an expansion of the proliferative population appropriate for E14. The even higher values of P for the SPP, 0.73-1.0, would expand this population rapidly in preparation for the high glial cell output to occur later in cerebral histogenesis.

Activity and expression pattern of cyclin-dependent kinase 5 in the embryonic mouse nervous system

L. H. Tsai, T. Takahashi, V. S. Caviness, Jr. and E. Harlow

Development 119 ( 4 ) 1029 - 40 1993.12

ISSN  0950-1991

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Cyclin-dependent kinase 5 (cdk5) was originally isolated on the basis of its close primary sequence homology to the human cdc2 serine/threonine kinase, the prototype of the cyclin-dependent kinases. While kinase activities of both cdc2 and cdk2 are detected in proliferating cells and are essential for cells to progress through the key transition points of the cell cycle, cdk5 kinase activity has been observed only in lysates of adult brain. In this study, we compared the activity and expression of cdk5 with that of cdc2 and cdk2 in the embryonic mouse forebrain. The expression and activity of cdk5 increased progressively as increasing numbers of cells exited the proliferative cycle. In contrast, the expression and activity of cdc2 and cdk2 were maximum at gestational day 11 (E11) when the majority of cells were proliferating and fell to barely detectable levels at E17 at the end of the cytogenetic period. Immunohistochemical studies showed that cdk5 is expressed in postmitotic neurons but not in glial cells or mitotically active cells. Expression of cdk5 was concentrated in fasciculated axons of postmitotic neurons. In contrast to other cell division cycle kinases to which it is closely related, cdk5 appears not to be expressed in dividing cells in the developing brain. These observations suggest that cdk5 may have a role in neuronal differentiation but not in the cell division cycle in the embryonic nervous system.

PCNA-binding to DNA at the G1/S transition in proliferating cells of the developing cerebral wall

T. Takahashi and V. S. Caviness, Jr.

J Neurocytol 22 ( 12 ) 1096 - 102 1993.12

ISSN  0300-4864

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Proliferating cell nuclear antigen is a nuclear protein essential to DNA synthesis in eukaryotic cells. It is known to form part of a multi-protein complex which binds to DNA from the outset of S-phase of the cell cycle. We define in this analysis the interval of proliferating cell nuclear antigen binding to DNA (strictly speaking, the interval through which proliferating cell nuclear antigen is stained immunohistochemically after ethanol fixation) with respect to the stages of the cell cycle in the intact mammalian brain. The epithelium of the developing cerebral wall is favourable for such an analysis because nuclei at the same stage of the cell division cycle are spatially aligned with each other at the same depth of the epithelium. Therefore spatial location of a nucleus within the epithelium is a reliable indicator of the stage of the cell cycle for that nucleus. Proliferating cell nuclear antigen-DNA binding in this epithelium is initiated in the final 5% (26 min) of G1-phase and continues through the initial 35% (1.3 h) of S-phase. This phasic pattern of proliferating cell nuclear antigen-DNA binding, as revealed for the first time in the intact cerebral wall, approximates closely the phasic pattern as it has been characterized until now only in vitro in vertebrate cell lines. This analysis illustrates the potential of the cerebral proliferative epithelium for study of the molecular events of the cell cycle under in vivo conditions of histogenetic regulation.

Cell cycle parameters and patterns of nuclear movement in the neocortical proliferative zone of the fetal mouse

T. Takahashi, R. S. Nowakowski and V. S. Caviness, Jr.

J Neurosci 13 ( 2 ) 820 - 33 1993.02

ISSN  0270-6474

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Cytogenesis is the critical determinant of the total number of neurons that contribute to the formation of the cerebral cortex and the rate at which the cells are produced. Two distinct cell populations constitute the proliferative population, a pseudostratified ventricular epithelium (PVE) lying within the ventricular zone (VZ) at the margin of the ventricle, and a secondary proliferative population that is intermixed with the PVE within the VZ but also is distributed through the overlying subventricular and intermediate zones of the cerebral wall. The present analysis, based upon cumulative S-phase labeling of the proliferative cells with 5-bromo-2'-deoxyuridine, is principally concerned with the PVE of the gestational-day-14 (E14) murine cerebral wall. It has immediate but also more far reaching general objectives. The most immediate objective, essential to the design and interpretation of later experiments, is to provide estimates of critical parameters of cytogenesis for the PVE. The growth fraction is virtually 100%. The lengths of the overall cell cycle, S-, G2+M-m, and G1-phases are 15.1 hr, 3.8 hr, 2 hr, and 9.3 hr, respectively. The PVE is homogeneous with respect to cell cycle length. For methodological considerations, these estimates are more accurate than estimates of the same parameters obtained in earlier analyses based upon S-phase labeling with tritiated thymidine. It is particularly with respect to a shorter length of S-phase determined here that the present values are different from those obtained with thymidine. At a more innovative level, the temporal and spatial resolution of nuclear movement made possible by the methods developed here will allow, in a way not previously attempted, a fine-grained tracking of nuclear movement as cells execute the successive stages of the cell cycle or exit the cycle subsequent to mitosis. Such observations are pertinent to our understanding of the regulatory mechanisms of neocortical histogenesis and the cell biological mechanisms that govern the proliferative cycle of the ventricular epithelium itself. It is known that the velocity of nuclear movement in the PVE is maximum in G2 (fourfold increase from S-phase) and minimum in M and early G1.(ABSTRACT TRUNCATED AT 400 WORDS)

BUdR as an S-phase marker for quantitative studies of cytokinetic behaviour in the murine cerebral ventricular zone

T. Takahashi, R. S. Nowakowski and V. S. Caviness, Jr.

J Neurocytol 21 ( 3 ) 185 - 97 1992.03

ISSN  0300-4864

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BUdR incorporation into replicating DNA, detected immunohistochemically, is used as an S-phase marker in the proliferative cell populations of the cerebral wall of the mouse embryo on the 14th gestational day (E14). The analysis initiates a series of studies concerned with the cytokinetic behaviour and cell output of proliferative populations involved in neocortical histogenesis. On E14 there are two periventricular proliferative zones in the cerebral wall. These are the ventricular and subventricular zones. The ventricular zone is a pseudostratified epithelium. DNA replication occurs with the cell nucleus in the outer zone of the epithelium and mitoses at the ventricular surface. Prior applications of BUdR for studies of cytogenesis in the CNS have been extended in two principal ways: (1) basic fuchsin was used as counterstain for BUdR-negative nuclei and (2) labelling indices were determined separately in strata or bins, 10 microns in height, through the full depth of the ventricular zone and overlying cerebral wall. It was established that a single injection of 50 micrograms g-1 into the pregnant dam was associated with labelling of 100% of nuclei in S-phase over an interval extending from 15 min to at least 2.0 h after injection. The zone where nuclei are undergoing S-phase (S-phase zone) extends through the outer four bins of the ventricular zone. The method has high quantitative reproducibility with an SE for labelling indices in bins within the S-phase zone less than 10% of the average values. Evidence is provided that BUdR incorporation is initiated with the nucleus in the outer aspect of the S-phase zone. The efficiency of incorporation of the marker is reduced as nuclei near the end of DNA replication and move to the inner aspect of the S-phase zone.

The alignment of migrating neural cells in relation to the murine neopallial radial glial fiber system

J. P. Misson, C. P. Austin, T. Takahashi, C. L. Cepko and V. S. Caviness, Jr.

Cereb Cortex 1 ( 3 ) 221 - 9 1991.05

ISSN  1047-3211

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The direction of neural cell migration in relation to the pattern of alignment of adjacent radial glial fibers has been studied in the developing neopallium of embryonic days 16-18 mouse embryos. The radial glial fibers were stained with RC2, a monoclonal antibody selective for cells of astroglial lineage in the developing murine brain. Migrating neural cells were stained histochemically with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) following retroviral transduction of the gene encoding beta-galactosidase into proliferating progenitors on E13. The leading processes and, generally, the somata of migrating neurons were found to be aligned in parallel with the radial glial fibers, despite substantial variations in the patterns of alignment of the fiber fascicles. The set of observations is consistent with the hypothesis that neural cell migration is supported by radial glial fibers.

Ontogeny of radial and other astroglial cells in murine cerebral cortex

J. P. Mission, T. Takahashi and V. S. Caviness, Jr.

Glia 4 ( 2 ) 138 - 48 1991

Joint Work,  ISSN  0894-1491

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Three cell forms of astroglial lineage populate the prenatal and early postnatal murine cerebral wall. In the present review we consider the ontogeny of these cell forms with respect to histogenetic events of the perinatal period. Classic bipolar radial glial cells predominate prior to E17. The bipolar coexist with monopolar radial forms in the perinatal period. Both bipolar and monopolar radial forms coexist with multipolar astrocytes in the course of the first postnatal week and are ultimately succeeded by the multipolar cells. The shift from bipolar to monopolar radial forms is initially coincident with translocation of somata of bipolar cells from the ventricular zone to the upper intermediate zone and cortical strata. Arborization appears to occur both at the growing tips and along the shaft of the processes of both bipolar and monopolar radial cell types. As arborization continues, the processes of the monopolar radial cells come to resemble those of the multipolar astrocytes. Eventually the radial cells are fully transformed into the multipolar astrocytic forms. During this period of transition, radial processes in the cortex appear to be degenerating, suggesting that regressive processes contribute to the cytologic transformation. This sequence of transformations begins late in the period of neuronal migration and continues through the early stages of growth and differentiation in the murine cerebral cortex. The signals that induce these changes may arise from differentiating neurons within the cortex. These transformations occur at a time when radial glial fibers are no longer required as guides for neuronal migration, and the glial population assumes new roles related to the development and operation of cortical neuronal circuits.

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