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Impaired cell cycle control of neuronal precursor cells in the neocortical primordium of presenilin-1-deficient mice.

Recent studies have implicated presenilin-1 (PS-1) in the processing of the amyloid precursor protein and Notch-1. We show that PS-1 has biological effects on differentiation and cell cycle control of neuronal precursor cells in vivo using PS-1-deficient mice. The expression of Class III beta-tubulin was upregulated throughout the neocortical primordia of PS-1-deficient E14 embryos, especially on the ventricular surface. The increased speed of migration of the immature neurons from the ventricular zone outward in the PS-1-deficient neocortical primordia was indicated by an in vivo bromodeoxyuridine (BrdU)-labeling assay and a DiI-labeling assay in slice culture. Furthermore, we investigated the cell cycle of neuronal precursor cells in the neocortical ventricular zone using an in vivo cumulative BrdU-labeling assay. The length of the cell cycle in the neocortical precursor cells of wild-type mice was 11.4 hr whereas that of the PS-1-deficient mice was 15.4 hr. Among all phases of the cell cycle, S-phase exhibited the most prominent change in length, increasing from 2.4 hr in the wild-type mice to 7.4 hr in the mutant mice. The distribution of beta-catenin was specifically affected in the ventricular zone of the PS-1-deficient mice. These findings suggest that PS-1 is involved in the differentiation and the cell cycle control of neuronal precursor cells in the ventricular proliferating zone of the neocortical primordium.

Pubmed ID: 12391611

Authors

  • Yuasa S
  • Nakajima M
  • Aizawa H
  • Sahara N
  • Koizumi K
  • Sakai T
  • Usami M
  • Kobayashi S
  • Kuroyanagi H
  • Mori H
  • Koseki H
  • Shirasawa T

Journal

Journal of neuroscience research

Publication Data

November 1, 2002

Associated Grants

None

Mesh Terms

  • Alleles
  • Animals
  • Cell Cycle
  • Cell Differentiation
  • Cell Movement
  • Cytoskeletal Proteins
  • Female
  • Fetus
  • Gene Expression Regulation, Developmental
  • Immunohistochemistry
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Neocortex
  • Neurons
  • Pregnancy
  • Presenilin-1
  • Receptor, Notch1
  • Receptors, Cell Surface
  • Signal Transduction
  • Stem Cells
  • Trans-Activators
  • Transcription Factors
  • beta Catenin