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

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

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282 Citations (Scopus)


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-, 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. It has been determined here that after the initiation of G1 there is a substantial differential in the time that postmitotic cells spend before they start their ascent toward the outer margin of the PVE; that is, some nuclei leave the ventricular surface shortly after mitosis (within 1.5 hr) while the more sluggish group of cells stays in the vicinity of the ventricular surface for up to 6 hr. Once postmitotic nuclei begin their ascent from the ventricular surface, they accelerate progressively through the outer half of the PVE. The analysis also shows that the cells are entering and leaving S-phase at equal rates, evidence in confirmation of the hypothesis that proliferation in the developing mouse cerebral wall at E14 is asynchronous.

Original languageEnglish
Pages (from-to)820-833
Number of pages14
JournalJournal of Neuroscience
Issue number2
Publication statusPublished - 1993
Externally publishedYes


  • Bromodeoxyuridine
  • Cell cycle
  • Mouse
  • Neocortical histogenesis
  • Neurogenesis
  • Proliferation
  • Subventricular zone
  • Ventricular zone

ASJC Scopus subject areas

  • Neuroscience(all)


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