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

• Published in: Journal of neuroscience research Vol. 70; no. 3; pp. 501 - 513
• Main Authors: Yuasa, Shigeki, Nakajima, Mitsunari, Aizawa, Hidenori, Sahara, Naruhiko, Koizumi, Ken-Ichi, Sakai, Tsuyoshi, Usami, Mihoko, Kobayashi, Shin-Ichiro, Kuroyanagi, Hidehito, Mori, Hiroshi, Koseki, Haruhiko, Shirasawa, Takuji
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01-11-2002
• Subjects: Alleles; Animals; beta Catenin; BrdU; cell cycle; Cell Cycle - genetics; Cell Differentiation - genetics; Cell Movement - genetics; Cytoskeletal Proteins - metabolism; Female; Fetus; Gene Expression Regulation, Developmental - physiology; Immunohistochemistry; Membrane Proteins - deficiency; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Knockout; Neocortex - abnormalities; Neocortex - cytology; Neocortex - metabolism; Neurons - cytology; Neurons - metabolism; Notch; Pregnancy; Presenilin-1; Receptor, Notch1; Receptors, Cell Surface; Signal Transduction - genetics; Stem Cells - cytology; Stem Cells - metabolism; Trans-Activators - metabolism; Transcription Factors; β-catenin
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.10430

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 β‐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 β–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. © 2002 Wiley‐Liss, Inc.