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Impaired cell cycle control of neuronal precursor cells in the neocortical primordium of presenilin‐1‐deficient mice
Author(s) -
Yuasa Shigeki,
Nakajima Mitsunari,
Aizawa Hidenori,
Sahara Naruhiko,
Koizumi KenIchi,
Sakai Tsuyoshi,
Usami Mihoko,
Kobayashi ShinIchiro,
Kuroyanagi Hidehito,
Mori Hiroshi,
Koseki Haruhiko,
Shirasawa Takuji
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10430
Subject(s) - primordium , cell cycle , microbiology and biotechnology , biology , precursor cell , bromodeoxyuridine , presenilin , in vivo , cell , neocortex , amyloid precursor protein , cell growth , medicine , neuroscience , biochemistry , alzheimer's disease , genetics , disease , gene
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.