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Ablation of BRaf Impairs Neuronal Differentiation in the Postnatal Hippocampus and Cerebellum

Please always quote using this URN: urn:nbn:de:bvb:20-opus-130304
  • This study focuses on the role of the kinase BRaf in postnatal brain development. Mice expressing truncated, non-functional BRaf in neural stem cell-derived brain tissue demonstrate alterations in the cerebellum, with decreased sizes and fuzzy borders of the glomeruli in the granule cell layer. In addition we observed reduced numbers and misplaced ectopic Purkinje cells that showed an altered structure of their dendritic arborizations in the hippocampus, while the overall cornus ammonis architecture appeared to be unchanged. In male miceThis study focuses on the role of the kinase BRaf in postnatal brain development. Mice expressing truncated, non-functional BRaf in neural stem cell-derived brain tissue demonstrate alterations in the cerebellum, with decreased sizes and fuzzy borders of the glomeruli in the granule cell layer. In addition we observed reduced numbers and misplaced ectopic Purkinje cells that showed an altered structure of their dendritic arborizations in the hippocampus, while the overall cornus ammonis architecture appeared to be unchanged. In male mice lacking BRaf in the hippocampus the size of the granule cell layer was normal at postnatal day 12 (P12) but diminished at P21, as compared to control littermates. This defect was caused by a reduced ability of dentate gyrus progenitor cells to differentiate into NeuN positive granule cell neurons. In vitro cell culture of P0/P1 hippocampal cells revealed that BRaf deficient cells were impaired in their ability to form microtubule-associated protein 2 positive neurons. Together with the alterations in behaviour, such as autoaggression and loss of balance fitness, these observations indicate that in the absence of BRaf all neuronal cellular structures develop, but neuronal circuits in the cerebellum and hippocampus are partially disturbed besides impaired neuronal generation in both structures.show moreshow less

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Metadaten
Author: Verena Pfeiffer, Rudolf Götz, Chaomei Xiang, Guadelupe Camarero, Attila Braun, Yina Zhang, Robert Blum, Helmut Heinsen, Bernhard Nieswandt, Ulf R. Rapp
URN:urn:nbn:de:bvb:20-opus-130304
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Klinische Neurobiologie
Medizinische Fakultät / Institut für Medizinische Strahlenkunde und Zellforschung
Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Fakultät für Biologie / Rudolf-Virchow-Zentrum
Medizinische Fakultät / Institut für Experimentelle Biomedizin
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2013
Volume:8
Issue:3
Pagenumber:e58259
Source:PLoS ONE 8(3): e58259. doi:10.1371/journal.pone.0058259
DOI:https://doi.org/10.1371/journal.pone.0058259
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:cerebellum; dentate gyrus; embryos; granule cells; hippocampus; neuronal dendrites; neuronal differentiation; neurons
Release Date:2016/07/06
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung