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Generation of neuronal variability and complexity

Abstract

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The production of specialized differentiated neurons derived from stem cells has been proposed as a revolutionary technology for regenerative medicine. However, few examples of specific neuronal cell differentiation have been described so far. Although stem-cell tissue replacement might be seemingly straightforward in other cases, the high degree of complexity of the nervous system raises the challenge of tissue replacement substantially. Understanding mechanisms of neuronal diversification will not only be relevant for therapeutic purposes but might also shed light on the differences in cognitive abilities, personality traits and psychiatric conditions observed in humans.

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Figure 1: Generation of somatic variability in the immune and neural systems.
Figure 2: Aneuploidy as a mechanism to alter gene expression in the CNS.
Figure 3: A model for generation of neuronal diversity by L1 retrotransposition.
Figure 4: Alternative start sites.
Figure 5: Alternative poly(A) sites.

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Acknowledgements

A.R.M. is a Pew Latin American Fellow. F.H.G. was supported by the Lookout Fund, and the National Institutes of Health National Institute on Aging and National Institute of Neurological Disorders and Stroke. The authors would like to thank M. L. Gage for editorial comments, and N. Spitzer and members of the Gage laboratory for critical comments on the manuscript. We regret that, owing to space limitations, we have been unable to refer to all of the primary literature and have had to rely instead, in many instances, on reviews.

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Muotri, A., Gage, F. Generation of neuronal variability and complexity. Nature 441, 1087–1093 (2006). https://doi.org/10.1038/nature04959

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