DOCSLIB.ORG

Major Depressive Disorder and Anxiety Disorders from the Glial Perspective: T Etiological Mechanisms, Intervention and Monitoring ⁎ Mari Silda,B, Edward S

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Major Depressive Disorder and Anxiety Disorders from the Glial Perspective: T Etiological Mechanisms, Intervention and Monitoring ⁎ Mari Silda,B, Edward S Neuroscience and Biobehavioral Reviews 83 (2017) 474–488 Contents lists available at ScienceDirect Neuroscience and Biobehavioral Reviews journal homepage: www.elsevier.com/locate/neubiorev Review article Major depressive disorder and anxiety disorders from the glial perspective: T Etiological mechanisms, intervention and monitoring ⁎ Mari Silda,b, Edward S. Ruthazerc, Linda Booija,b,d, a Concordia University, 7141 Sherbrooke St W., H4B 1R6 Montreal, Québec, Canada b Sainte-Justine Hospital Research Center, 3175 Côte-Sainte-Catherine, H3T 1C5 Montreal, Québec, Canada c Montreal Neurological Institute, McGill University, 3801 University St., H3A 2B4 Montreal, Québec, Canada d Department of Psychiatry, McGill University, 1033 Pine Avenue W., H3A 1A1 Montreal, Québec, Canada ARTICLE INFO ABSTRACT Keywords: Despite intense ongoing research efforts, the etiology of psychiatric disorders remains incompletely understood. Glia Among biological factors playing a role in Major Depressive Disorder (MDD) and Anxiety Disorders (ANX), Major depressive disorder emerging evidence points to the relevance of different types of glia cells and efficient neuron-glia interactions. Anxiety disorders Here, we review recent findings highlighting the involvement of central nervous system (CNS) glia in MDD and Early trauma ANX etiology and treatment response. Additionally, several relatively underexplored topics will be discussed: (1) Brain imaging glial response to non-pharmacological therapies, (2) impact of early life adversity on glia, (3) influence of Astrocyte Oligodendrocyte lifestyle factors on glia in the context of MDD and ANX, and (4) monitoring glial functions in patients. It can be Microglia concluded that despite the sequence of events is still unclear, alterations in glial cell types are common and Radial glia somewhat overlapping in ANX, MDD and corresponding animal models. Furthermore, glia are responsive to a Psychiatric disorders variety of treatment and lifestyle options. Looking forward, new research developments can lead to novel types of therapeutic or symptom-relieving approaches targeting glia. 1. Introduction over the years (Booij et al., 2015), it has also become increasingly clear that alterations in monoamine systems are not sufficient to explain the Psychiatric illnesses constitute a major disease burden in the world, full spectra of MDD and ANX phenotypes and treatment responses. with Major Depressive Disorder (MDD; all abbreviations found in In the search for underlying mechanisms, the importance of non- Table 1) being the single leading cause of time loss due to disability for neuronal cell types, most notably immune cells and glia, has been in- both males and females (Kessler et al., 2005b; World Health creasingly recognized (Di Benedetto and Rupprecht, 2013). Glia com- Organization, 2016). MDD has lifetime prevalence of around 16%, and prise several morphologically and functionally distinct cell types that this number is projected to increase (Kessler et al., 2003; Lopez et al., are found in central and peripheral nervous system and are at least as 2006; World Health Organization, 2016). Anxiety disorders (ANX) have abundant as neurons (Hilgetag and Barbas, 2009). Glia are crucially lifetime prevalence of around 28% (Kessler et al., 2005a). While MDD involved in the regulation of nervous system development (Rakic, 1971, and ANX are highly heterogeneous diagnostic categories (Nandi et al., 1972), formation of vasculature and blood-brain-barrier (BBB) 2009), they display significant comorbidity and may share some etio- (Siqueira et al., 2017), signal transmission (Baumann and Pham-Dinh, logical mechanisms (Avenevoli et al., 2001; Gorwood, 2004; Ruscio and 2001; Bunge et al., 1962; Pomeranz et al., 1968), synapse formation Khazanov, 2017). (Ango et al., 2008; Elmariah et al., 2005; Pfrieger and Barres, 1997; Sild A fundamental obstacle to treating MDD and ANX effectively has et al., 2016) and neuroplasticity (Araque et al., 1999; Panatier et al., been an incomplete understanding of the underlying biological me- 2006; Papouin et al., 2017). Such variety of functions has prompted chanisms and of exactly how drugs and other interventions work at the research of glial participation in the etiology of psychiatric disorders molecular-cellular level. The earliest evidence-based theories on MDD and as possible drug targets (Di Benedetto and Rupprecht, 2013; Manev and ANX focused on a deficit of monoamines, in particular, serotonin et al., 2003). Accumulating evidence points to glial alterations in all (Dell'osso and Lader, 2013; Hyman, 2013). While monoaminergic the- major psychiatric conditions, although schizophrenia and MDD have ories of the etiological mechanisms of these diseases have been refined received the most research attention in this context (Bernstein et al., ⁎ Corresponding author at: Concordia University, Dept. of Psychology, 7141 Sherbrooke St. West, SP 253.03, Montreal, Québec H4B 1R6, Canada. E-mail addresses: [email protected] (M. Sild), [email protected] (E.S. Ruthazer), [email protected] (L. Booij). http://dx.doi.org/10.1016/j.neubiorev.2017.09.014 Received 3 July 2017; Received in revised form 8 August 2017; Accepted 11 September 2017 Available online 14 September 2017 0149-7634/ © 2017 Elsevier Ltd. All rights reserved. M. Sild et al. Neuroscience and Biobehavioral Reviews 83 (2017) 474–488 Table 1 multiple perspectives of how glial cells may participate in the etiology Abbreviations. and treatment of MDD and ANX. This review starts with a brief introduction to central nervous Abbreviation Meaning system (CNS) glia development and subtypes, followed by an overview 5-HT 5-Hydroxytryptamine of findings of glial alterations in MDD, ANX and related animal models. ACC Anterior Cingulate Cortex Next, since exposure to early life adversity is a major risk factor for AD Antidepressant development of MDD and ANX in later life (Heim and Nemeroff, 2001; ANX Anxiety Disorders ff ATP Adenosine Triphosphate Kessler et al., 2010), a section is devoted to glial responses to di erent BBB Blood-Brain Barrier types of early life stress. We will discuss how glia are affected by BDNF Brain-Derived Neurotrophic Factor pharmacological and non-pharmacological MDD and ANX treatments CNS Central Nervous System and lifestyle factors. Some means of monitoring glial function in living EE Environmental Enrichment humans will be covered. The overarching hypothesis of this review FGF Fibroblast Growth Factor GAD Generalized Anxiety Disorder article is that glial alterations that are present in MDD and ANX may GDNF Glial Cell Line-Derived Neurotrophic Factor serve as important cues for the disease etiology and as targets for GFAP Glial Fibrillary Acidic Protein therapeutic approaches. GLAST Glutamate Aspartate Transporter GLT-1 Glutamate Transporter 1 GR Glucocorticoid Receptor 2. Overview of central nervous system glia and their functions HDAC Histone Deacetylase HDACi Histone Deacetylase Inhibitor Central nervous system (CNS) glia, which include astrocytes, oli- LPS Bacterial Lipopolysaccharide − MDD Major Depressive Disorder godendrocytes, NG2 cells, radial glia, microglia and ependymal cells mPFC Medial Prefrontal Cortex carry out a number of crucial support and regulatory functions in the NG2 Neural/Glial Antigen 2 mature CNS that are outlined in Table 2. Importantly, glia are also OCD Obsessive Compulsive Disorder critically involved in the development of the CNS from very early OD Oligodendrocyte PFC Prefrontal Cortex prenatal stages. Radial glia derive directly from the nervous system RG Radial Glia stem cells (neuroepithelial cells) and are already present when the first SAD Seasonal Affective Disorder immature neurons form in the CNS (in humans around gestational week SNRI Serotonin-Norepinephrine Reuptake Inhibitor 4) (Barry et al., 2014; Gotz and Huttner, 2005; Rakic, 1972). From there SSRI Selective Serotonin Reuptake Inhibitor on, radial glia serve as guidance substrates for neuronal migration TSPO 18 kDa Translocator Protein VEGF Vascular Endothelial Growth Factor (Rakic, 1972), direct growing axons to their target locations (Norris and VGF VGF Nerve Growth Factor Inducible Kalil, 1991; Silver et al., 1982) and induce angiogenesis (Siqueira et al., 2017) thus structurally organizing the CNS neural network. Further- more, radial glia themselves are progenitors for neurons (Kriegstein and 2015; Dallerac and Rouach, 2016; Di Benedetto and Rupprecht, 2013; Alvarez-Buylla, 2009; Noctor et al., 2001) and other glia (i.e., astro- Elsayed and Magistretti, 2015; Laskaris et al., 2016; Rajkowska and cytes, oligodendrocytes and ependymal cells) that appear slightly later Stockmeier, 2013; Rial et al., 2015; Takahashi and Sakurai, 2013; Wang in the development (Budday et al., 2015; Pinto and Gotz, 2007). In et al., 2017). contrast, microglia are not derived from radial glia but from yolk sac fi The present review focuses speci cally on glial roles in the most macrophage precursors, and enter the brain around the time of neu- common mental disorders, MDD and ANX. Furthermore, the notion that rogenesis (Ginhoux et al., 2010; Reemst et al., 2016). Deviations in glial these two psychiatric conditions are often co-morbid may imply some functions during development have already been shown to cause major commonalities in glial alterations. However, roles of glia have been neurodevelopmental diseases like lissencephaly (Wu and Wang, 2012). much less explored in ANX than in MDD. In addition to a broad over- Lissencephaly patients experience
Load more

Recommended publications
  • Neuregulin 1–Erbb2 Signaling Is Required for the Establishment of Radial Glia and Their Transformation Into Astrocytes in Cerebral Cortex
    Neuregulin 1–erbB2 signaling is required for the establishment of radial glia and their transformation into astrocytes in cerebral cortex Ralf S. Schmid*, Barbara McGrath*, Bridget E. Berechid†, Becky Boyles*, Mark Marchionni‡, Nenad Sˇ estan†, and Eva S. Anton*§ *University of North Carolina Neuroscience Center and Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599; †Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510; and ‡CeNes Pharamceuticals, Inc., Norwood, MA 02062 Communicated by Pasko Rakic, Yale University School of Medicine, New Haven, CT, January 27, 2003 (received for review December 12, 2002) Radial glial cells and astrocytes function to support the construction mine whether NRG-1-mediated signaling is involved in radial and maintenance, respectively, of the cerebral cortex. However, the glial cell development and differentiation in the cerebral cortex. mechanisms that determine how radial glial cells are established, We show that NRG-1 signaling, involving erbB2, may act in maintained, and transformed into astrocytes in the cerebral cortex are concert with Notch signaling to exert a critical influence in the not well understood. Here, we show that neuregulin-1 (NRG-1) exerts establishment, maintenance, and appropriate transformation of a critical role in the establishment of radial glial cells. Radial glial cell radial glial cells in cerebral cortex. generation is significantly impaired in NRG mutants, and this defect can be rescued by exogenous NRG-1. Down-regulation of expression Materials and Methods and activity of erbB2, a member of the NRG-1 receptor complex, leads Clonal Analysis to Study NRG’s Role in the Initial Establishment of to the transformation of radial glial cells into astrocytes.
    [Show full text]
  • Endogenous Radial Glial Cells Support Regenerating Axons After Spinal
    Cellular, molecular, and developmental neuroscience 871 Endogenous radial glial cells support regenerating axons after spinal cord transection Hiroshi Nomuraa, Howard Kimb, Andrea Mothea, Tasneem Zahirb, Iris Kulbatskia, Cindi M. Morsheadc, Molly S. Shoichetb and Charles H. Tatora During the development of central nervous system, radial NeuroReport 21:871–876 c 2010 Wolters Kluwer Health | glial cells support target-specific neuronal migration. Lippincott Williams & Wilkins. We recently reported that after implantation of chitosan NeuroReport 2010, 21:871–876 channels with complete spinal cord transection, the tissue bridging the spinal cord stumps contained axons and radial Keywords: channel implantation, chitosan, radial glial cell, spinal cord injury, spinal cord transection glial cells. The purpose of this study was to clarify the role of the radial glial cells in the tissue bridges. Chitosan aToronto Western Research Institute, Toronto Western Hospital, bDepartment of Chemical Engineering and Applied Chemistry and cDepartment of Surgery and channels were implanted in rats with thoracic spinal Institute of Medical Sciences, University of Toronto, Terrence Donnelly Centre for cord transection. After 14 weeks, all animals had tissue Cellular and Biomolecular Research, Toronto, Ontario, Canada bridges in the channels that contained many radial glial Correspondence to Charles H. Tator, MD, PhD, Toronto Western Research cells in longitudinal arrangement, some of which were Institute, Toronto Western Hospital, Room 12-423, McLaughlin Wing, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada in contact with axons in the bridges. We suggest that Tel: + 1 416 603 5889; fax: + 1 416 603 5298; e-mail:[email protected] radial glial cells can guide regenerating axons across Received 25 May 2010 accepted 25 June 2010 the bridge in the channel after spinal cord transection.
    [Show full text]
  • Extracellular Matrix: Functions in the Nervous System
    Downloaded from http://cshperspectives.cshlp.org/ on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press Extracellular Matrix: Functions in the Nervous System Claudia S. Barros, Santos J. Franco, and Ulrich Mu¨ller The Scripps Research Institute, Department of Cell Biology, Dorris Neuroscience Center, La Jolla, California 92037 Correspondence: [email protected] An astonishing number of extracellular matrix glycoproteins are expressed in dynamic patterns in the developing and adult nervous system. Neural stem cells, neurons, and glia express receptors that mediate interactions with specific extracellular matrix molecules. Functional studies in vitro and genetic studies in mice have provided evidence that the extra- cellular matrix affects virtually all aspects of nervous system development and function. Here we will summarize recent findings that have shed light on the specific functions of defined extracellular matrix molecules on such diverse processes as neural stem cell differentiation, neuronal migration, the formation of axonal tracts, and the maturation and function of syn- apses in the peripheral and central nervous system. xtracellular matrix (ECM) glycoproteins are NEURAL STEM CELL BEHAVIOR AND Ewidely expressed in the developing and adult NEURONAL MIGRATION nervous system. Tremendous progress has been made in defining the roles of specific ECM com- NSCs give rise to neurons and glia, and the ponents in controlling the behavior of neurons ECM provides a microenvironment that mod- and glia (Sanes 1989; Reichardt and Tomaselli ulates NSC behavior (Perris and Perissinotto 1991; Venstrom and Reichardt 1993; Milner 2000; Sobeih and Corfas 2002; Zimmermann and Campbell 2002; Nakamoto et al. 2004). and Dours-Zimmermann 2008). Radial glial Here, we will provide an overview of ECM func- cells (RGCs) of the developing central nervous tions in the nervous system, emphasizing recent system (CNS) are a well-studied class of NSCs findings that have shed light on the mechanisms (Fig.
    [Show full text]
  • First Division, 44 Head Neural Induction and Maintenance, 45–46 Trunk
    Index A3B5ϩ/PSA-NCAMϩ cells, 165 first division, 44 Ablation studies, 78 head neural induction and maintenance, 45–46 Acetylcholine (ACh), 295–296 trunk neural induction, 46–50 Acetylcholine esterase (AChE), 284 regional patterning, 50–57 Acetylcholine receptor (AChR) channels, 276 Antibodies that promote remyelination, 182 Acetylcholine receptor inducing activity (ARIA), 294 Apaf-1, 322–323 Acetylcholine receptors (AChRs), 273, 276, 278–281, 284, 290, 293, 309 Apoptosis-inducing factor (AIF), 319 distribution, 285 Apoptosis pathway, 353 types of, 269, 271 Apoptotic cell death, 318, 319; see also Programmed cell death Achaete-scute homologue ash1, 97 Ara-C (cytosine arabinoside), 205 Actin, retrograde flow of, 246 Architectonic maps, 396–397 Actin-binding protein filamin 1 (filamin-␣), 225 Astrocyte development Active zones (AZ), 270, 275, 279–280 in cerebellum, 208 Activin, 9, 10 in forebrain Adhesion, tactile, 377 pathways of, giving rise to different types of astrocytes, 207–208 Adhesion proteins, synaptic, 300–305 is not uniform across different regions of CNS, 199 Adhesive cell-surface signals, 251 in spinal cord, 208–209 Adrenoleukodystrophy, 173 Astrocyte genesis, interplay of multiple pathways contributes to, 216 Age-related alterations in neurogenesis, developmental mechanisms Astrocyte lineages underlying, 354–357 model of, 212 Age-related cytoarchitectural changes in nervous system, 350–351 in vitro, heterogeneity within, 211 Age-related molecular changes in nervous system, 351 Astrocyte precursor cells (APCs), 212–213 Age-related
    [Show full text]
  • Glia As Architects of Central Nervous System Formation and Function*
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Science Manuscript Author . Author manuscript; Manuscript Author available in PMC 2019 April 12. Published in final edited form as: Science. 2018 October 12; 362(6411): 181–185. doi:10.1126/science.aat0473. Glia as Architects of Central Nervous System Formation and Function* Nicola J. Allen1,* and David A. Lyons2,* 1. Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA 2. Centre for Discovery Brain Sciences, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK Abstract Glia constitute roughly half of the cells of the central nervous system (CNS), but were long- considered static bystanders to its formation and function. Here we provide an overview of how the diverse and dynamic functions of glial cells orchestrate essentially all aspects of nervous system formation and function. Radial glia, astrocytes, oligodendrocyte progenitor cells, oligodendrocytes and microglia each influence nervous system development, from neuronal birth, migration, axon specification and growth, through to circuit assembly and synaptogenesis. As neural circuits mature, distinct glia fulfil key roles in synaptic communication, plasticity, homeostasis, and networklevel activity, through dynamic monitoring and alteration of CNS structure and function. Continued elucidation of glial cell biology, and the dynamic interactions of neurons and glia, will enrich our understanding of nervous system formation, health and function. Introduction Cursed perhaps by the incorrect assertion of Virchow in 1846 that the brain contains a connective structure called “nervenkitt”, the mundane notion of glia as glue (deriving from Greek) emerged, and stuck (1). This is despite the fact that soon after Virchow’s “discovery” of glia, the famous neuroanatomists of the late 19th and early 20th century had not only identified the major glia of the CNS, but speculated with keen foresight on their potential diverse functions (1).
    [Show full text]
  • Allen-Lyons-Science-Glia-Review
    Edinburgh Research Explorer Glia as architects of central nervous system formation and function Citation for published version: Allen, NJ & Lyons, DA 2018, 'Glia as architects of central nervous system formation and function', Science, vol. 362, no. 6411, pp. 181-185. https://doi.org/10.1126/science.aat0473 Digital Object Identifier (DOI): 10.1126/science.aat0473 Link: Link to publication record in Edinburgh Research Explorer Document Version: Peer reviewed version Published In: Science General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 07. Oct. 2021 Glia as Architects of Central Nervous System Formation and Function Nicola J Allen1,* and David A Lyons2,* 1. Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA 2. Centre for Discovery Brain Sciences, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK *Correspondence: [email protected] (N.J.A.), [email protected] (D.A.L.) 1 Abstract Glia constitute roughly half of the cells of the central nervous system (CNS), but were long- considered static bystanders to its formation and function.
    [Show full text]
  • Glial Cell Regulation of Neuronal Activity and Blood Flow in the Retina by Release Rstb.Royalsocietypublishing.Org of Gliotransmitters
    Downloaded from http://rstb.royalsocietypublishing.org/ on May 25, 2015 Glial cell regulation of neuronal activity and blood flow in the retina by release rstb.royalsocietypublishing.org of gliotransmitters Eric A. Newman Department of Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church Street SE, Minneapolis, Review MN 55455, USA Cite this article: Newman EA. 2015 Glial cell Astrocytes in the brain release transmitters that actively modulate neuronal regulation of neuronal activity and blood flow excitability and synaptic efficacy. Astrocytes also release vasoactive agents in the retina by release of gliotransmitters. that contribute to neurovascular coupling. As reviewed in this article, Mu¨ller Phil. Trans. R. Soc. B 370: 20140195. cells, the principal retinal glial cells, modulate neuronal activity and blood http://dx.doi.org/10.1098/rstb.2014.0195 flow in the retina. Stimulated Mu¨ ller cells release ATP which, following its conversion to adenosine by ectoenzymes, hyperpolarizes retinal ganglion cells by activation of A1 adenosine receptors. This results in the opening of Accepted: 23 March 2015 G protein-coupled inwardly rectifying potassium (GIRK) channels and small conductance Ca2þ-activated Kþ (SK) channels. Tonic release of ATP also con- One contribution of 16 to a discussion meeting tributes to the generation of tone in the retinal vasculature by activation of P2X issue ‘Release of chemical transmitters from receptors on vascular smooth muscle cells. Vascular tone is lost when glial cells are poisoned with the gliotoxin fluorocitrate. The glial release of vasoac- cell bodies and dendrites of nerve cells’. tive metabolites of arachidonic acid, including prostaglandin E2 (PGE2)and epoxyeicosatrienoic acids (EETs), contributes to neurovascular coupling in Subject Areas: the retina.
    [Show full text]
  • Genes with Human-Specific Features Are Primarily Involved with Brain, Immune and Metabolic Evolution Mainá Bitar1* , Stefanie Kuiper2, Elizabeth A
    Bitar et al. BMC Bioinformatics 2019, 20(Suppl 9):406 https://doi.org/10.1186/s12859-019-2886-2 RESEARCH Open Access Genes with human-specific features are primarily involved with brain, immune and metabolic evolution Mainá Bitar1* , Stefanie Kuiper2, Elizabeth A. O’Brien1 and Guy Barry1,3 From Annual Meeting of the Bioinformatics Italian Society (BITS 2018) Turin, Italy. 27 - 29 June 2018 Abstract Background: Humans have adapted to widespread changes during the past 2 million years in both environmental and lifestyle factors. This is evident in overall body alterations such as average height and brain size. Although we can appreciate the uniqueness of our species in many aspects, molecular variations that drive such changes are far from being fully known and explained. Comparative genomics is able to determine variations in genomic sequence that may provide functional information to better understand species-specific adaptations. A large number of human- specific genomic variations have been reported but no currently available dataset comprises all of these, a problem which contributes to hinder progress in the field. Results: Here we critically update high confidence human-specific genomic variants that mostly associate with protein-coding regions and find 856 related genes. Events that create such human-specificity are mainly gene duplications, the emergence of novel gene regions and sequence and structural alterations. Functional analysis of these human-specific genes identifies adaptations to brain, immune and metabolic systems to be highly involved. We further show that many of these genes may be functionally associated with neural activity and generating the expanded human cortex in dynamic spatial and temporal contexts.
    [Show full text]
  • Radial Glial Cell–Neuron Interaction Directs Axon Formation at the Opposite Side of the Neuron from the Contact Site
    The Journal of Neuroscience, October 28, 2015 • 35(43):14517–14532 • 14517 Development/Plasticity/Repair Radial Glial Cell–Neuron Interaction Directs Axon Formation at the Opposite Side of the Neuron from the Contact Site Chundi Xu, Yasuhiro Funahashi, Takashi Watanabe, Tetsuya Takano, Shinichi Nakamuta, Takashi Namba, and Kozo Kaibuchi Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan How extracellular cues direct axon–dendrite polarization in mouse developing neurons is not fully understood. Here, we report that the radial glial cell (RGC)–cortical neuron interaction directs axon formation at the opposite side of the neuron from the contact site. N-cadherin accumulates at the contact site between the RGC and cortical neuron. Inhibition of the N-cadherin-mediated adhesion decreases this oriented axon formation in vitro, and disrupts the axon–dendrite polarization in vivo. Furthermore, the RGC–neuron interaction induces the polarized distribution of active RhoA at the contacting neurite and active Rac1 at the opposite neurite. Inhibition of Rho–Rho-kinase signaling in a neuron impairs the oriented axon formation in vitro, and prevents axon–dendrite polarization in vivo. Collectively, these results suggest that the N-cadherin-mediated radial glia–neuron interaction determines the contacting neurite as the leading process for radial glia-guided neuronal migration and directs axon formation to the opposite side acting through the Rho family GTPases. Key words: axon formation; axon–dendrite
    [Show full text]
  • Extracellular Regulation of the Mitotic Spindle and Fate Determinants Driving Asymmetric Cell Division
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Results Manuscript Author Probl Cell Differ Manuscript Author . Author manuscript; available in PMC 2018 January 01. Published in final edited form as: Results Probl Cell Differ. 2017 ; 61: 351–373. doi:10.1007/978-3-319-53150-2_16. Extracellular Regulation of the Mitotic Spindle and Fate Determinants Driving Asymmetric Cell Division Prestina Smith, Mark Azzam, and Lindsay Hinck Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA 95064, USA Abstract Stem cells use mode of cell division, symmetric (SCD) versus asymmetric (ACD), to balance expansion with self-renewal and the generation of daughter cells with different cell fates. Studies in model organisms have identified intrinsic mechanisms that govern this process, which involves partitioning molecular components between daughter cells, frequently through the regulation of the mitotic spindle. Research performed in vertebrate tissues is revealing both conservation of these intrinsic mechanisms and crucial roles for extrinsic cues in regulating the frequency of these divisions. Morphogens and positional cues, including planar cell polarity proteins and guidance molecules, regulate key signaling pathways required to organize cell/ECM contacts and spindle pole dynamics. Noncanonical WNT7A/VANGL2 signaling governs asymmetric cell division and the acquisition of cell fates through spindle pole orientation in satellite stem cells of regenerating muscle fibers. During cortical neurogenesis, the same pathway regulates glial cell fate determination by regulating spindle size, independent of its orientation. Sonic hedgehog (SHH) stimulates the symmetric expansion of cortical stem and cerebellar progenitor cells and contributes to cell fate acquisition in collaboration with Notch and Wnt signaling pathways.
    [Show full text]
  • Microglial Migration and Adhesion Molecules During Embryonic Brain Development Sophie Smolders
    Microglial migration and adhesion molecules during embryonic brain development Sophie Smolders To cite this version: Sophie Smolders. Microglial migration and adhesion molecules during embryonic brain development. Neurons and Cognition [q-bio.NC]. Université Pierre et Marie Curie - Paris VI; Universiteit Hasselt (1970-..), 2017. English. NNT : 2017PA066533. tel-01890177 HAL Id: tel-01890177 https://tel.archives-ouvertes.fr/tel-01890177 Submitted on 8 Oct 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Université Pierre et Marie Curie Universiteit Hasselt CERVEAU - COGNITION - COMPORTEMENT Neurosciences Paris Seine, UPMC INSERM S 1130, CNRS UMR 8246 Development of Spinal Cord Organization La migration des microglies et les molécules adhésives au cours du développement embryonnaire du cerveau Par Sophie Smolders Thèse de doctorat de Neurosciences Dirigée par Pascal Legendre et Bert Brône Présentée et soutenue publiquement le 30 octobre 2017 Devant un jury composé de : Prof. dr Marcel Ameloot, Universiteit Hasselt, Diepenbeek, Belgium, Maître de conférences Prof. dr. Bert Brône, Universiteit Hasselt, Diepenbeek, Belgium, promotor Dr. Pascal Legendre, Université Pierre et Marie Curie, Paris, France, promotor Prof. dr. Niels Hellings, Universiteit Hasselt, Diepenbeek, Belgium Dr. Isabelle Dusart, Université Pierre et Marie Curie, Paris, France Dr.
    [Show full text]
  • Schwann Cell Precursors; Multipotent Glial Cells in Embryonic Nerves
    REVIEW published: 26 March 2019 doi: 10.3389/fnmol.2019.00069 Schwann Cell Precursors; Multipotent Glial Cells in Embryonic Nerves Kristjan R. Jessen* and Rhona Mirsky Department of Cell and Developmental Biology, University College London, London, United Kingdom The cells of the neural crest, often referred to as neural crest stem cells, give rise to a number of sub-lineages, one of which is Schwann cells, the glial cells of peripheral nerves. Crest cells transform to adult Schwann cells through the generation of two well defined intermediate stages, the Schwann cell precursors (SCP) in early embryonic nerves, and immature Schwann cells (iSch) in late embryonic and perinatal nerves. SCP are formed when neural crest cells enter nascent nerves and form intimate relationships with axons, a diagnostic feature of glial cells. This involves large-scale changes in gene expression, including the activation of established glial cell markers. Like early glia in the CNS, radial glia, SCP retain developmental multipotency and contribute to other crest- derived lineages during embryonic development. SCP, as well as closely related cells termed boundary cap cells, and later stages of the Schwann cell lineage have all been implicated as the tumor initiating cell in NF1 associated neurofibromas. iSch are formed from SCP in a process that involves the appearance of additional differentiation markers, autocrine survival circuits, cellular elongation, a formation of endoneurial connective Edited by: tissue and basal lamina. Finally, in peri- and post-natal nerves, iSch are reversibly induced Virginie Neirinckx, by axon-associated signals to form the myelin and non-myelin Schwann cells of adult Luxembourg Institute of Health (LIH), Luxembourg nerves.
    [Show full text]