Neuronal Plasticity and Diversity

PL2 Neuronal Plasticity and Diversity ○Fred Gage1 Laboratory of Genetics, Salk Institute1 The first part of the talk will focus on evidence supporting the birth and maturation of new neurons in the adult dentate gyrus of the hippocampus in the mammalian brain. The mechanism by which the cells integrate and become functional will be discussed. In addition, the potential functional significance for adult neurogenesis in the context of the normal function of the hippocampus will be discussed. In the second part of the talk I will focus on the recent finding that LINE-1 (Long Interspersed Nucleotide Elements-1 or L1) retroelements are active in somatic neuronal progenitor cells (NPCs) providing an additional mechanism for neuronal diversification. Together with their mutated relatives, retroelement 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.

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