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      Death of developing neurons: New insights and implications for connectivity

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          Abstract

          The concept that target tissues determine the survival of neurons has inspired much of the thinking on neuronal development in vertebrates, not least because it is supported by decades of research on nerve growth factor (NGF) in the peripheral nervous system (PNS). Recent discoveries now help to understand why only some developing neurons selectively depend on NGF. They also indicate that the survival of most neurons in the central nervous system (CNS) is not simply regulated by single growth factors like in the PNS. Additionally, components of the cell death machinery have begun to be recognized as regulators of selective axonal degeneration and synaptic function, thus playing a critical role in wiring up the nervous system.

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          Most cited references81

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          Caspases 3 and 7: key mediators of mitochondrial events of apoptosis.

          The current model of apoptosis holds that upstream signals lead to activation of downstream effector caspases. We generated mice deficient in the two effectors, caspase 3 and caspase 7, which died immediately after birth with defects in cardiac development. Fibroblasts lacking both enzymes were highly resistant to both mitochondrial and death receptor-mediated apoptosis, displayed preservation of mitochondrial membrane potential, and had defective nuclear translocation of apoptosis-inducing factor (AIF). Furthermore, the early apoptotic events of Bax translocation and cytochrome c release were also delayed. We conclude that caspases 3 and 7 are critical mediators of mitochondrial events of apoptosis.
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            Cell death during development of the nervous system.

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              Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice.

              New neurons are continually generated in the adult hippocampus, but the important question, whether adult neurogenesis is transient or leads to the lasting presence of new neurons, has not yet been answered. Dividing cells were labeled with bromodeoxyuridine (BrdU) and were investigated by means of immunofluorescence and confocal microscopy at several time-points 1 day to 11 months thereafter. BrdU-labeled neurons remained stable in number and in their relative position in the granule cell layer over at least 11 months. This finding implies that the addition of new neurons is not transient and that their final number and localization are determined early. By contrast, expression of immature markers beta-III-tubulin and doublecortin in BrdU-labeled cells, peaked early after division and was not detectable after 4 weeks. In transgenic mice expressing enhanced green fluorescent protein under the nestin promoter none of the BrdU/nestin-positive cells early after division expressed the mature marker NeuN, confirming that no dividing neurons were detected. These new data suggest that new neurons are recruited early from the pool of proliferating progenitor cells and lead to a lasting effect of adult neurogenesis.
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                Author and article information

                Journal
                J Cell Biol
                J. Cell Biol
                jcb
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                11 November 2013
                : 203
                : 3
                : 385-393
                Affiliations
                [1 ]Biozentrum, University of Basel, 4056 Basel, Switzerland
                [2 ]Institute of Molecular Biology and Biotechnology, GR-70013 Heraklion, Crete, Greece
                Author notes
                Correspondence to Yves-Alain Barde: bardey@ 123456cardiff.ac.uk

                Y.-A. Barde’s present address is Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, Wales, UK.

                Article
                201306136
                10.1083/jcb.201306136
                3824005
                24217616
                912400cb-da75-41fe-ba5a-1f55e60a82e4
                © 2013 Dekkers et al.

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                : 24 June 2013
                : 3 October 2013
                Categories
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                Reviews
                Review
                Cell biology in neuroscience

                Cell biology
                Cell biology

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