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      Neurogenesis in the embryonic and adult brain: same regulators, different roles

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          Abstract

          Neurogenesis persists in adult mammals in specific brain areas, known as neurogenic niches. Adult neurogenesis is highly dynamic and is modulated by multiple physiological stimuli and pathological states. There is a strong interest in understanding how this process is regulated, particularly since active neuronal production has been demonstrated in both the hippocampus and the subventricular zone (SVZ) of adult humans. The molecular mechanisms that control neurogenesis have been extensively studied during embryonic development. Therefore, we have a broad knowledge of the intrinsic factors and extracellular signaling pathways driving proliferation and differentiation of embryonic neural precursors. Many of these factors also play important roles during adult neurogenesis, but essential differences exist in the biological responses of neural precursors in the embryonic and adult contexts. Because adult neural stem cells (NSCs) are normally found in a quiescent state, regulatory pathways can affect adult neurogenesis in ways that have no clear counterpart during embryogenesis. BMP signaling, for instance, regulates NSC behavior both during embryonic and adult neurogenesis. However, this pathway maintains stem cell proliferation in the embryo, while it promotes quiescence to prevent stem cell exhaustion in the adult brain. In this review, we will compare and contrast the functions of transcription factors (TFs) and other regulatory molecules in the embryonic brain and in adult neurogenic regions of the adult brain in the mouse, with a special focus on the hippocampal niche and on the regulation of the balance between quiescence and activation of adult NSCs in this region.

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          Mechanisms and functional implications of adult neurogenesis.

          The generation of new neurons is sustained throughout adulthood in the mammalian brain due to the proliferation and differentiation of adult neural stem cells. In this review, we discuss the factors that regulate proliferation and fate determination of adult neural stem cells and describe recent studies concerning the integration of newborn neurons into the existing neural circuitry. We further address the potential significance of adult neurogenesis in memory, depression, and neurodegenerative disorders such as Alzheimer's and Parkinson's disease.
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            The cell biology of neurogenesis.

            During the development of the mammalian central nervous system, neural stem cells and their derivative progenitor cells generate neurons by asymmetric and symmetric divisions. The proliferation versus differentiation of these cells and the type of division are closely linked to their epithelial characteristics, notably, their apical-basal polarity and cell-cycle length. Here, we discuss how these features change during development from neuroepithelial to radial glial cells, and how this transition affects cell fate and neurogenesis.
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              Stem cells and niches: mechanisms that promote stem cell maintenance throughout life.

              Niches are local tissue microenvironments that maintain and regulate stem cells. Long-predicted from mammalian studies, these structures have recently been characterized within several invertebrate tissues using methods that reliably identify individual stem cells and their functional requirements. Although similar single-cell resolution has usually not been achieved in mammalian tissues, principles likely to govern the behavior of niches in diverse organisms are emerging. Considerable progress has been made in elucidating how the microenvironment promotes stem cell maintenance. Mechanisms of stem cell maintenance are key to the regulation of homeostasis and likely contribute to aging and tumorigenesis when altered during adulthood.
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                Author and article information

                Contributors
                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                27 November 2014
                2014
                : 8
                : 396
                Affiliations
                [1]Department of Molecular Neurobiology, MRC National Institute for Medical Research London, UK
                Author notes

                Edited by: Jens Christian Schwamborn, University of Luxembourg, Luxembourg

                Reviewed by: Tao Sun, Cornell University Weill Medical College, USA; Mikio Hoshino, National Center of Neurology and Psychiatry, Japan

                *Correspondence: Noelia Urbán and François Guillemot, Department of Molecular Neurobiology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK e-mail: nurban@ 123456nimr.mrc.ac.uk ; fguille@ 123456nimr.mrc.ac.uk

                This article was submitted to the journal Frontiers in Cellular Neuroscience.

                Article
                10.3389/fncel.2014.00396
                4245909
                25505873
                95507ac9-8da1-4818-a2c4-2eb1d3712462
                Copyright © 2014 Urbán and Guillemot.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 September 2014
                : 05 November 2014
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 259, Pages: 19, Words: 18796
                Categories
                Neuroscience
                Review Article

                Neurosciences
                hippocampal neurogenesis,development of the hippocampus,regulation of adult neurogenesis,neural stem cell quiescence,niche signals in adult neurogenesis

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