title: Gene amplification during differentiation of mammalian neural stem cells in vitro and in vivo.
abstract: In development of amphibians and flies, gene amplification is one of mechanisms to increase gene expression. In mammalian cells, gene amplification seems to be restricted to tumorigenesis and acquiring of drug-resistance in cancer cells. Here, we report a complex gene amplification pattern in mouse neural progenitor cells during differentiation with approximately 10% of the genome involved. Half of the amplified mouse chromosome regions overlap with amplified regions previously reported in human neural progenitor cells, indicating conserved mechanisms during differentiation. Using fluorescence in situ hybridization, we verified the amplification in single cells of primary mouse mesencephalon E14 (embryonic stage) neurosphere cells during differentiation. In vivo we confirmed gene amplifications of the TRP53 gene in cryosections from mouse embryos at stage E11.5. Gene amplification is not only a cancer-related mechanism but is also conserved in evolution, occurring during differentiation of mammalian neural stem cells.
authors.affiliation: Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Fischer
authors.affiliation: Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany.|Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.affiliation: Department of Anatomy and Cell Biology, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Raslan
authors.affiliation: Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.affiliation: Department of Anatomy and Cell Biology, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Meier
authors.affiliation: Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D055028:Comparative Genomic Hybridization; D005347:Fibroblasts / Q000378:metabolism; D005784:Gene Amplification; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D005819:Genetic Markers; D016678:Genome; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008636:Mesencephalon; D051379:Mice; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000166:cytology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D005819:Genetic Markers; D016159:Tumor Suppressor Protein p53
keywords: array-CGH; genomic stability; in vivo; neurosphere