The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination.
Growth factors of the gp130 family promote oligodendrocyte differentiation, and viability, and myelination, but their mechanisms of action are incompletely understood. Here, we show that these effects are coordinated, in part, by the transcriptional activator Krüppel-like factor-6 (Klf6). Klf6 is ra...
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Public Library of Science (PLoS)
2016-05-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1002467&type=printable |
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| author | Benjamin M Laitman Linnéa Asp John N Mariani Jingya Zhang Jia Liu Setsu Sawai Candice Chapouly Sam Horng Elisabeth G Kramer Nesanet Mitiku Hannah Loo Natalie Burlant Xiomara Pedre Yuko Hara German Nudelman Elena Zaslavsky Young-Min Lee David A Braun Q Richard Lu Goutham Narla Cedric S Raine Scott L Friedman Patrizia Casaccia Gareth R John |
| author_facet | Benjamin M Laitman Linnéa Asp John N Mariani Jingya Zhang Jia Liu Setsu Sawai Candice Chapouly Sam Horng Elisabeth G Kramer Nesanet Mitiku Hannah Loo Natalie Burlant Xiomara Pedre Yuko Hara German Nudelman Elena Zaslavsky Young-Min Lee David A Braun Q Richard Lu Goutham Narla Cedric S Raine Scott L Friedman Patrizia Casaccia Gareth R John |
| author_sort | Benjamin M Laitman |
| collection | DOAJ |
| description | Growth factors of the gp130 family promote oligodendrocyte differentiation, and viability, and myelination, but their mechanisms of action are incompletely understood. Here, we show that these effects are coordinated, in part, by the transcriptional activator Krüppel-like factor-6 (Klf6). Klf6 is rapidly induced in oligodendrocyte progenitors (OLP) by gp130 factors, and promotes differentiation. Conversely, in mice with lineage-selective Klf6 inactivation, OLP undergo maturation arrest followed by apoptosis, and CNS myelination fails. Overlapping transcriptional and chromatin occupancy analyses place Klf6 at the nexus of a novel gp130-Klf-importin axis, which promotes differentiation and viability in part via control of nuclear trafficking. Klf6 acts as a gp130-sensitive transactivator of the nuclear import factor importin-α5 (Impα5), and interfering with this mechanism interrupts step-wise differentiation. Underscoring the significance of this axis in vivo, mice with conditional inactivation of gp130 signaling display defective Klf6 and Impα5 expression, OLP maturation arrest and apoptosis, and failure of CNS myelination. |
| format | Article |
| id | doaj-art-2dfa39249e6546189fb8f3c3d17cf445 |
| institution | OA Journals |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2016-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-2dfa39249e6546189fb8f3c3d17cf4452025-08-20T02:15:40ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852016-05-01145e100246710.1371/journal.pbio.1002467The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination.Benjamin M LaitmanLinnéa AspJohn N MarianiJingya ZhangJia LiuSetsu SawaiCandice ChapoulySam HorngElisabeth G KramerNesanet MitikuHannah LooNatalie BurlantXiomara PedreYuko HaraGerman NudelmanElena ZaslavskyYoung-Min LeeDavid A BraunQ Richard LuGoutham NarlaCedric S RaineScott L FriedmanPatrizia CasacciaGareth R JohnGrowth factors of the gp130 family promote oligodendrocyte differentiation, and viability, and myelination, but their mechanisms of action are incompletely understood. Here, we show that these effects are coordinated, in part, by the transcriptional activator Krüppel-like factor-6 (Klf6). Klf6 is rapidly induced in oligodendrocyte progenitors (OLP) by gp130 factors, and promotes differentiation. Conversely, in mice with lineage-selective Klf6 inactivation, OLP undergo maturation arrest followed by apoptosis, and CNS myelination fails. Overlapping transcriptional and chromatin occupancy analyses place Klf6 at the nexus of a novel gp130-Klf-importin axis, which promotes differentiation and viability in part via control of nuclear trafficking. Klf6 acts as a gp130-sensitive transactivator of the nuclear import factor importin-α5 (Impα5), and interfering with this mechanism interrupts step-wise differentiation. Underscoring the significance of this axis in vivo, mice with conditional inactivation of gp130 signaling display defective Klf6 and Impα5 expression, OLP maturation arrest and apoptosis, and failure of CNS myelination.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1002467&type=printable |
| spellingShingle | Benjamin M Laitman Linnéa Asp John N Mariani Jingya Zhang Jia Liu Setsu Sawai Candice Chapouly Sam Horng Elisabeth G Kramer Nesanet Mitiku Hannah Loo Natalie Burlant Xiomara Pedre Yuko Hara German Nudelman Elena Zaslavsky Young-Min Lee David A Braun Q Richard Lu Goutham Narla Cedric S Raine Scott L Friedman Patrizia Casaccia Gareth R John The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination. PLoS Biology |
| title | The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination. |
| title_full | The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination. |
| title_fullStr | The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination. |
| title_full_unstemmed | The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination. |
| title_short | The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination. |
| title_sort | transcriptional activator kruppel like factor 6 is required for cns myelination |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1002467&type=printable |
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