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Retrotransposition and neuronal diversity| old_uid | 2405 |
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| title | Retrotransposition and neuronal diversity |
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| start_date | 2007/03/13 |
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| schedule | 12h |
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| online | no |
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| details | Invit. Bernard Lakowski, lakowski@pasteur.fr, 01 45 68 87 08 |
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| summary | Brain formation is an incredibly wasteful process. About half of the nerve cells created in a developing brain have died by the time that brain has formed. Many researchers believe that the cells that live and those that die is decided by a process similar to natural selection. Cells with the right properties in the right places flourish; those without wither. But natural selection requires random variation to generate the various properties. The recent finding that LINE-1 (Long Interspersed Nucleotide Elements-1 or L1) retroelements are active in somatic neuronal progenitor cells (NPCs) provided an additional mechanism for neuronal diversification (Muotri et al Nature, 2005 and Muotri & Gage, Nature 2006). Together with their mutated relatives, retroelements sequences constitute 45% of the mammalian genome with L1 elements alone representing 20%. The fact that L1 can retrotranspose in a defined window of neuronal differentiation, changing the genetic information in single neurons in an arbitrary fashion, allows the brain to develop in distinctly different ways. This characteristic of variety and flexibility may contribute to the uniqueness of an individual brain. However, the molecular mechanism that regulates L1 expression in NPCs is not completely understood. L1s are likely silenced in neural stem cells due to Sox2-mediated transcription repression. Down-regulation of Sox2 accompanies chromatin modifications, such as DNA de-methylation and histone acetylation, which in turn may trigger neuronal differentiation. The characterization of somatic neuronal diversification will not only be relevant for the understanding of brain complexity and neuronal organization in mammals but may also shed light on the differences in cognitive abilities, personality traits and many psychiatric conditions observed in humans. |
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| responsibles | Granon |
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