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      Moving the Shh Source over Time: What Impact on Neural Cell Diversification in the Developing Spinal Cord?

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          Abstract

          A substantial amount of data has highlighted the crucial influence of Shh signalling on the generation of diverse classes of neurons and glial cells throughout the developing central nervous system. A critical step leading to this diversity is the establishment of distinct neural progenitor cell domains during the process of pattern formation. The forming spinal cord, in particular, has served as an excellent model to unravel how progenitor cells respond to Shh to produce the appropriate pattern. In recent years, considerable advances have been made in our understanding of important parameters that control the temporal and spatial interpretation of the morphogen signal at the level of Shh-receiving progenitor cells. Although less studied, the identity and position of Shh source cells also undergo significant changes over time, raising the question of how moving the Shh source contributes to cell diversification in response to the morphogen. Here, we focus on the dynamics of Shh-producing cells and discuss specific roles for these time-variant Shh sources with regard to the temporal events occurring in the receiving field.

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          Oligodendrocyte Development and Plasticity.

          Oligodendrocyte precursor cells (OPCs) originate in the ventricular zones (VZs) of the brain and spinal cord and migrate throughout the developing central nervous system (CNS) before differentiating into myelinating oligodendrocytes (OLs). It is not known whether OPCs or OLs from different parts of the VZ are functionally distinct. OPCs persist in the postnatal CNS, where they continue to divide and generate myelinating OLs at a decreasing rate throughout adult life in rodents. Adult OPCs respond to injury or disease by accelerating their cell cycle and increasing production of OLs to replace lost myelin. They also form synapses with unmyelinated axons and respond to electrical activity in those axons by generating more OLs and myelin locally. This experience-dependent "adaptive" myelination is important in some forms of plasticity and learning, for example, motor learning. We review the control of OL lineage development, including OL population dynamics and adaptive myelination in the adult CNS.
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            Regional astrocyte allocation regulates CNS synaptogenesis and repair.

            Astrocytes, the most abundant cell population in the central nervous system (CNS), are essential for normal neurological function. We show that astrocytes are allocated to spatial domains in mouse spinal cord and brain in accordance with their embryonic sites of origin in the ventricular zone. These domains remain stable throughout life without evidence of secondary tangential migration, even after acute CNS injury. Domain-specific depletion of astrocytes in ventral spinal cord resulted in abnormal motor neuron synaptogenesis, which was not rescued by immigration of astrocytes from adjoining regions. Our findings demonstrate that region-restricted astrocyte allocation is a general CNS phenomenon and reveal intrinsic limitations of the astroglial response to injury.
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              Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway.

              The Shh signaling pathway is required in many mammalian tissues for embryonic patterning, cell proliferation and differentiation. In addition, inappropriate activation of the pathway has been implicated in many human tumors. Based on transfection assays and gain-of-function studies in frog and mouse, the transcription factor Gli1 has been proposed to be a major mediator of Shh signaling. To address whether this is the case in mouse, we generated a Gli1 null allele expressing lacZ. Strikingly, Gli1 is not required for mouse development or viability. Of relevance, we show that all transcription of Gli1 in the nervous system and limbs is dependent on Shh and, consequently, Gli1 protein is normally not present to transduce initial Shh signaling. To determine whether Gli1 contributes to the defects seen when the Shh pathway is inappropriately activated and Gli1 transcription is induced, Gli1;Ptc double mutants were generated. We show that Gli1 is not required for the ectopic activation of the Shh signaling pathway or to the early embryonic lethal phenotype in Ptc null mutants. Of significance, we found instead that Gli2 is required for mediating some of the inappropriate Shh signaling in Ptc mutants. Our studies demonstrate that, in mammals, Gli1 is not required for Shh signaling and that Gli2 mediates inappropriate activation of the pathway due to loss of the negative regulator Ptc.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                J Dev Biol
                J Dev Biol
                jdb
                Journal of Developmental Biology
                MDPI
                2221-3759
                12 April 2017
                June 2017
                : 5
                : 2
                : 4
                Affiliations
                Centre de Biologie du Développement (CBD) CNRS/UPS, Centre de Biologie Intégrative (CBI), Université de Toulouse, 31520 Toulouse, France
                Author notes
                [* ]Correspondence: cathy.danesin@ 123456univ-tlse3.fr (C.D.); catherine.soula@ 123456univ-tlse3.fr (C.S.); Tel.: +33-5-61-55-64-23 (C.D. & C.S.)
                Article
                jdb-05-00004
                10.3390/jdb5020004
                5831764
                29615562
                0ef18cc0-1492-4767-a7a3-43e9f4f2c4f7
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 February 2017
                : 06 April 2017
                Categories
                Review

                sonic hedgehog,neural tube patterning,notochord,medial floor plate,lateral floor plate,neurons,glial cells,amniotes,zebrafish

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