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DC Field | Value | Language |
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dc.contributor | Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP | - |
dc.contributor.author | PFEIFFER, Verena | - |
dc.contributor.author | GOETZ, Rudolf | - |
dc.contributor.author | CAMARERO, Guadelupe | - |
dc.contributor.author | HEINSEN, Helmut | - |
dc.contributor.author | BLUM, Robert | - |
dc.contributor.author | RAPP, Ulf Ruediger | - |
dc.date.accessioned | 2018-07-05T18:09:50Z | - |
dc.date.available | 2018-07-05T18:09:50Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | PLOS ONE, v.13, n.3, article ID e0192067, 21p, 2018 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://observatorio.fm.usp.br/handle/OPI/27191 | - |
dc.description.abstract | RAF kinases are major constituents of the mitogen activated signaling pathway, regulating cell proliferation, differentiation and cell survival of many cell types, including neurons. In mammals, the family of RAF proteins consists of three members, ARAF, BRAF, and CRAF. Ablation of CRAF kinase in inbred mouse strains causes major developmental defects during fetal growth and embryonic or perinatal lethality. Heterozygous germline mutations in CRAF result in Noonan syndrome, which is characterized by neurocognitive impairment that may involve hippocampal physiology. The role of CRAF signaling during hippocampal development and generation of new postnatal hippocampal granule neurons has not been examined and may provide novel insight into the cause of hippocampal dysfunction in Noonan syndrome. In this study, by crossing CRAF-deficiency to CD-1 outbred mice, a CRAF mouse model was established which enabled us to investigate the interplay of neural progenitor proliferation and postmitotic differentiation during adult neurogenesis in the hippo campus. Albeit the general morphology of the hippocampus was unchanged, CRAF-deficient mice displayed smaller granule cell layer (GCL) volume at postnatal day 30 (P30). In CRAF-deficient mice a substantial number of abnormal, chromophilic, fast dividing cells were found in the subgranular zone (SGZ) and hilus of the dentate gyrus (DG), indicating that CRAF signaling contributes to hippocampal neural progenitor proliferation. CRAF-deficient neural progenitor cells showed an increased cell death rate and reduced neuronal maturation. These results indicate that CRAF function affects postmitotic neural cell differentiation and points to a critical role of CRAF-dependent growth factor signaling pathway in the postmitotic development of adult-born neurons. | - |
dc.description.sponsorship | Deutsche Forschungsgemeinschaft [1048] | - |
dc.language.iso | eng | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.relation.ispartof | Plos One | - |
dc.rights | openAccess | - |
dc.subject.other | activated protein-kinase | - |
dc.subject.other | central-nervous-system | - |
dc.subject.other | adult neurogenesis | - |
dc.subject.other | dentate gyrus | - |
dc.subject.other | b-raf | - |
dc.subject.other | noonan-syndrome | - |
dc.subject.other | stem-cells | - |
dc.subject.other | c-raf | - |
dc.subject.other | knockout mice | - |
dc.subject.other | a-raf | - |
dc.title | Impaired neuronal maturation of hippocampal neural progenitor cells in mice lacking CRAF | - |
dc.type | article | - |
dc.rights.holder | Copyright PUBLIC LIBRARY SCIENCE | - |
dc.identifier.doi | 10.1371/journal.pone.0192067 | - |
dc.identifier.pmid | 29590115 | - |
dc.subject.wos | Multidisciplinary Sciences | - |
dc.type.category | original article | - |
dc.type.version | publishedVersion | - |
hcfmusp.author.external | PFEIFFER, Verena:Univ Wurzburg, Inst Anat & Cell Biol, Koellikerstr 6, Wurzburg, Germany; Univ Wurzburg, Inst Med Radiat & Cell Res MSZ, Versbacher Str 5, Wurzburg, Germany | - |
hcfmusp.author.external | GOETZ, Rudolf:Univ Wurzburg, Inst Med Radiat & Cell Res MSZ, Versbacher Str 5, Wurzburg, Germany; Univ Hosp Wurzburg, Inst Clin Neurobiol, Versbacher Str 5, Wurzburg, Germany | - |
hcfmusp.author.external | CAMARERO, Guadelupe:Univ Wurzburg, Inst Med Radiat & Cell Res MSZ, Versbacher Str 5, Wurzburg, Germany | - |
hcfmusp.author.external | BLUM, Robert:Univ Hosp Wurzburg, Inst Clin Neurobiol, Versbacher Str 5, Wurzburg, Germany | - |
hcfmusp.author.external | RAPP, Ulf Ruediger:Univ Wurzburg, Inst Med Radiat & Cell Res MSZ, Versbacher Str 5, Wurzburg, Germany; Max Planck Inst Heart & Lung Res, Dept Lung Dev & Remodeling, Pk Str 1, Bad Nauheim, Germany | - |
hcfmusp.description.articlenumber | e0192067 | - |
hcfmusp.description.issue | 3 | - |
hcfmusp.description.volume | 13 | - |
hcfmusp.origem | WOS | - |
hcfmusp.origem.id | WOS:000428603100002 | - |
hcfmusp.origem.id | 2-s2.0-85044865514 | - |
hcfmusp.publisher.city | SAN FRANCISCO | - |
hcfmusp.publisher.country | USA | - |
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dc.description.index | MEDLINE | - |
hcfmusp.citation.scopus | 3 | - |
hcfmusp.scopus.lastupdate | 2024-03-29 | - |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - HC/Outros |
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