PMID:12391611

Citation	Yuasa, S, Nakajima, M, Aizawa, H, Sahara, N, Koizumi, K, Sakai, T, Usami, M, Kobayashi, S, Kuroyanagi, H, Mori, H, Koseki, H and Shirasawa, T (2002) Impaired cell cycle control of neuronal precursor cells in the neocortical primordium of presenilin-1-deficient mice. J. Neurosci. Res. 70:501-13
Abstract	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.
Links	PubMed Online version:10.1002/jnr.10430
Keywords	Alleles; Animals; 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; Pregnancy; Presenilin-1; Receptor, Notch1; Receptors, Cell Surface; Signal Transduction/genetics; Stem Cells/cytology; Stem Cells/metabolism; Trans-Activators/metabolism; Transcription Factors; beta Catenin
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