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

http://www.ncbi.nlm.nih.gov/pubmed/12391611

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 RIS Download

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

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Mouse Genome Informatics (Data, Gene Annotation)

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