DOCSLIB.ORG

The Case of the Scribble Polarity Module in Asymmetric Neuroblast Division in Development and Tumorigenesis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Case of the Scribble Polarity Module in Asymmetric Neuroblast Division in Development and Tumorigenesis International Journal of Molecular Sciences Review The Case of the Scribble Polarity Module in Asymmetric Neuroblast Division in Development and Tumorigenesis Ana Carmena Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas/Universidad Miguel Hernández, 03550 Sant Joan d’Alacant, Alicante, Spain; [email protected] Received: 20 March 2020; Accepted: 17 April 2020; Published: 20 April 2020 Abstract: The Scribble polarity module is composed by Scribble (Scrib), Discs large 1 (Dlg1) and Lethal (2) giant larvae (L(2)gl), a group of highly conserved neoplastic tumor suppressor genes (TSGs) from flies to humans. Even though the Scribble module has been profusely studied in epithelial cell polarity, the number of tissues and processes in which it is involved is increasingly growing. Here we discuss the role of the Scribble module in the asymmetric division of Drosophila neuroblasts (NBs), as well as the underlying mechanisms by which those TSGs act in this process. Finally, we also describe what we know about the consequences of mutating these genes in impairing the process of asymmetric NB division and promoting tumor-like overgrowth. Keywords: Scribble polarity module; asymmetric cell division; neuroblasts; tumorigenesis; Drosophila 1. The Scribble Polarity Module The Scribble polarity module is composed by Scribble (Scrib), Discs large 1 (Dlg1) and lethal (2) giant larvae (L(2)gl), all of which represent highly conserved neoplastic tumor suppressor genes (TSGs) from flies to humans [1–4]. l(2)gl alleles were first isolated in Drosophila by Bridges in 1930s [5], but their malignant mutant phenotype, an extensive overproliferation and tissue disorganization in imaginal epithelia and adult brain anlagen (optic lobe), was described years later in an spontaneous l(2)gl mutation (l(2)gl4)[6]. Thus, l(2)gl was the first example of a TSG, even before the term “tumor suppressor gene” came on stage [7–9], although the existence of a recessive class of cancer genes (“recessive oncogenes”) had already been suggested by Harris’ cell fusion experiments and Knudson’s retinoblastoma studies [10,11]. dlg1 was isolated few years later in a screen for mutant phenotypes in the imaginal discs that altered their morphology. dlg1 mutants showed hypertrophied and disorganized discs, a phenotype, as the authors pointed out, very similar to that shown by l(2)gl4 mutants (Stewart et al. 1972). The third component of the module, scrib, was identified twenty years ago in a screen for mutations that altered the embryonic epithelial architecture in Drosophila [12]. scrib phenotype was identical to that shown by l(2)gl and dlg1 mutants in embryonic, follicular and imaginal disc epithelia, strongly suggesting that all three genes acted in the same pathway to regulate cell growth and cell polarity [13]. A collaborative activity in a single pathway of scrib, dlg1 and l(2)gl was confirmed by epistatic and strong genetic interactions between them, as well as by their cell localization and activity interdependence [13]. This, along with other previous works showed that the three neoplastic TSGs of the Scribble module were also key regulators of apico-basal cell polarity [3,12–16]. In epithelia, mutants in all these neoplastic TSGs lead to massive overgrowth and tumor formation in a homozygote condition, i.e., when the whole epithelial tissue is mutant for the TSG. However, mutant clones for each of these TSGs, scrib, dlg1 and l(2)gl, do not overgrow, have poor survival, and are finally eliminated by cell competition, a process in which the surrounding wild-type cells activate a Int. J. Mol. Sci. 2020, 21, 2865; doi:10.3390/ijms21082865 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2020, 21, x FOR PEER REVIEW 2 of 13 Int. J. Mol. Sci. 2020, 21, 2865 2 of 12 l(2)gl, do not overgrow, have poor survival, and are finally eliminated by cell competition, a process in which the surrounding wild-type cells activate a Jun N-terminal kinase (JNK)-mediated apoptosis Junin the N-terminal mutant cells kinase [17–22]. (JNK)-mediated An oncogenic, apoptosis activated in the form mutant of Ras, cells Ras [17V12–, 22can]. prevent An oncogenic, the cell activated death in formthese ofTSG Ras, singleRasV1 mutant2, can clones prevent by the transforming cell death inthe these pro-apoptotic TSG single fu mutantnction of clones JNK into by transforminga pro-growth theeffect, pro-apoptotic inducing the function formation of JNK of big into neoplastic a pro-growth tumoral effect, masses inducing [18,19,21,23]. the formation More recently, of big neoplastic though, tumoralit has been masses shown, [18, 19for,21 four,23]. different More recently, l(2)gl null though, mutant it has alleles, been shown,that l(2)gl for foursingle di mutantfferent l(2)gl clonesnull in mutanteye-antennal alleles, discs that behavel(2)gl single differently mutant from clones scrib/dlg1 in eye-antennal clones, in discs the sense behave that di fftheyerently are not from eliminatedscrib/dlg1 clones,by cell incompetition. the sense that In theyfact, arel(2)gl not clones eliminated overproliferate by cell competition. without affecting In fact, l(2)gl cell polarityclones overproliferate by repressing withoutthe Hippo aff ectingsignaling cell pathway polarity by[24,25] repressing. Intriguingly, the Hippo it has signaling been found pathway that not [24 ,only25]. Intriguingly,l(2)gl but also it dlg1 has beensingle found mutant that clones, not only in antennall(2)gl but discs, also overgrowdlg1 single by mutant activating clones, the inRas-MAPK antennal discs,signaling overgrow pathway, by activatingwhile scrib the clones Ras-MAPK do not signaling [26]. Thus, pathway, it might while be scribthat clonesthe consequences do not [26]. of Thus, losing it might these be TSGs that theare consequencescontext-dependent, of losing and thesethat the TSGs induced are context-dependent, levels of signaling andpathways, that the such induced as JNK levels or Ras-MAPK, of signaling in pathways,the mutant such clones as determine JNK or Ras-MAPK, the apoptosis in the or mutantsurvival clones of the determineclone. the apoptosis or survival of the clone.Scrib, Dlg1, and L(2)gl are all cytoplasmic, membrane-associated proteins that co-localize to the baso-lateralScrib, Dlg1, domain and L(2)glof epithelial are all cytoplasmic,cells. Scrib membrane-associatedand Dlg1 are multi proteinsPDZ (PSD-95/Dlg1/ZO-1) that co-localize to thedomain-containing baso-lateral domain proteins of epithelialthat act as cells.scaffolds, Scrib whereas and Dlg1 L(2)gl are is multia non-muscle PDZ (PSD-95 myosin/Dlg1 II binding/ZO-1) domain-containingprotein with WD-40 proteins repeats that and, act as unlike scaffolds, Scrib whereas and L(2)glDlg1, isis acortically non-muscle uniform myosin (Figure II binding 1) protein[1,3,12,22,27,28]. with WD-40 repeats and, unlike Scrib and Dlg1, is cortically uniform (Figure1)[ 1,3,12,22,27,28]. FigureFigure 1.1.The The Scribble Scribble polarity polarity module. module. The The modular modular structure structure of the of proteins the proteins belonging belonging to the Scribble to the module,Scribble Scrib,module, Dlg1, Scrib, and L(2)gl,Dlg1, isand shown. L(2)gl, The is LAP shown. (Leucine-rich The LAP repeats (Leucine-rich Aand PDZ repeats domains) Aand protein PDZ Scribdomains) and theprotein MAGUK Scrib (Membraneand the MAGUK Associated (Membran GUanylatee Associated Kinase) GUanylate protein Dlg1 Kinase) both containprotein PDZDlg1 domainsboth contain and additionalPDZ domains motifs, and such additional as 16 Leucine-Rich-Repeats motifs, such as 16 Leucine-Rich-Rep (LRRs, in Scrib) oreats a Src(LRRs, Homology in Scrib) 3 andor a aSrc GUuanylate Homology Kinase 3 and (SH3 a GUuanylate and GUK domains, Kinase (SH3 in Dlg1). and L(2)glGUK containsdomains, WD-40 in Dlg1). repeats. L(2)gl Conserved contains phosphorylationWD-40 repeats. Conserved sites are shown phosphorylation in both L(2)gl sites and are Scrib. shown in both L(2)gl and Scrib. SomeSome physicalphysical interactionsinteractions betweenbetween thethe ScribbleScribble modulemodule proteinsproteins havehave beenbeen describeddescribed inin mammalsmammals [[29,30],29,30], andand in inDrosophila Drosophilathe the adaptor adaptor protein protein GUK-holder GUK-holder (Gukh) (Gukh) links links Scrib Scrib and Dlg1and Dlg1 [31]. In[31]. addition, In addition, multiple multiple proteins proteins directly directly interact intera to eachct ofto theeach core of componentsthe core components of the Scribble of the module Scribble in manymodule di ffinerent many cellular different contexts cellular and contexts processes, and and processes, the number and ofthe interacting number of proteins interacting is increasingly proteins is growingincreasingly [4]. Amonggrowing these [4]. proteins Among are th includedese proteins regulators are included of different regulato typesrs of of cell different polarity,cytoskeleton, types of cell vesicularpolarity, tracytoskeleton,fficking, tissue vesicular growth, trafficking, as well as tissue cell proliferation, growth, as well survival, as cell and proliferation, migration [survival,3,4]. Some and of thesemigration proteins [3,4]. might Some be of potentialthese proteins novel might regulators be po oftential asymmetric novel regulators neuroblast of (NB)asymmetric division, neuroblast another process(NB) division, in which another the Scribble process module in which isalso the Scribble operative. module is also operative. 2. Beyond Epithelia: The Scribble Polarity Module in Neuroblasts 2. Beyond Epithelia: The Scribble
Load more

Recommended publications
  • Early Neuronal and Glial Fate Restriction of Embryonic Neural Stem Cells
    The Journal of Neuroscience, March 5, 2008 • 28(10):2551–2562 • 2551 Development/Plasticity/Repair Early Neuronal and Glial Fate Restriction of Embryonic Neural Stem Cells Delphine Delaunay,1,2 Katharina Heydon,1,2 Ana Cumano,3 Markus H. Schwab,4 Jean-Le´on Thomas,1,2 Ueli Suter,5 Klaus-Armin Nave,4 Bernard Zalc,1,2 and Nathalie Spassky1,2 1Inserm, Unite´ 711, 75013 Paris, France, 2Institut Fe´de´ratif de Recherche 70, Faculte´deMe´decine, Universite´ Pierre et Marie Curie, 75013 Paris, France, 3Inserm, Unite´ 668, Institut Pasteur, 75724 Paris Cedex 15, France, 4Max-Planck-Institute of Experimental Medicine, D-37075 Goettingen, Germany, and 5Institute of Cell Biology, Swiss Federal Institute of Technology (ETH), ETH Ho¨nggerberg, CH-8093 Zu¨rich, Switzerland The question of how neurons and glial cells are generated during the development of the CNS has over time led to two alternative models: either neuroepithelial cells are capable of giving rise to neurons first and to glial cells at a later stage (switching model), or they are intrinsically committed to generate one or the other (segregating model). Using the developing diencephalon as a model and by selecting a subpopulation of ventricular cells, we analyzed both in vitro, using clonal analysis, and in vivo, using inducible Cre/loxP fate mapping, the fate of neuroepithelial and radial glial cells generated at different time points during embryonic development. We found that, during neurogenic periods [embryonic day 9.5 (E9.5) to 12.5], proteolipid protein ( plp)-expressing cells were lineage-restricted neuronal precursors, but later in embryogenesis, during gliogenic periods (E13.5 to early postnatal), plp-expressing cells were lineage-restricted glial precursors.
    [Show full text]
  • Drosophila Aurora-A Kinase Inhibits Neuroblast Self-Renewal by Regulating Apkc/Numb Cortical Polarity and Spindle Orientation
    Downloaded from genesdev.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation Cheng-Yu Lee,1,3,4 Ryan O. Andersen,1,3 Clemens Cabernard,1 Laurina Manning,1 Khoa D. Tran,1 Marcus J. Lanskey,1 Arash Bashirullah,2 and Chris Q. Doe1,5 1Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, Oregon 97403, USA; 2Department of Human Genetics, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA Regulation of stem cell self-renewal versus differentiation is critical for embryonic development and adult tissue homeostasis. Drosophila larval neuroblasts divide asymmetrically to self-renew, and are a model system for studying stem cell self-renewal. Here we identify three mutations showing increased brain neuroblast numbers that map to the aurora-A gene, which encodes a conserved kinase implicated in human cancer. Clonal analysis and time-lapse imaging in aurora-A mutants show single neuroblasts generate multiple neuroblasts (ectopic self-renewal). This phenotype is due to two independent neuroblast defects: abnormal atypical protein kinase C (aPKC)/Numb cortical polarity and failure to align the mitotic spindle with the cortical polarity axis. numb mutant clones have ectopic neuroblasts, and Numb overexpression partially suppresses aurora-A neuroblast overgrowth (but not spindle misalignment). Conversely, mutations that disrupt spindle alignment but not cortical polarity have increased neuroblasts. We conclude that Aurora-A and Numb are novel inhibitors of neuroblast self-renewal and that spindle orientation regulates neuroblast self-renewal.
    [Show full text]
  • Embryonic Development of Glial Cells and Their Junctions in the Locust Central Nervous System'
    0270.6474/85/0501-0117$02.00/O The Journal of Neuroscience Copyright 0 Society for Neuroscience Vol. 5, No. 1, pp. 117-127 Printed in U.S.A. January 1985 EMBRYONIC DEVELOPMENT OF GLIAL CELLS AND THEIR JUNCTIONS IN THE LOCUST CENTRAL NERVOUS SYSTEM’ LESLEY S. SWALES AND NANCY J. LANE The A.F.R.C. Unit of Insect Neurophysiology and Pharmacology, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, United Kingdom Received February 14, 1984; Revised June 6, 1984; Accepted July 23, 1984 Abstract The embryonic development of the specialized glial cells that form the perineurial blood-brain barrier in the locust CNS ha’s been studied by freeze-fracture and tracer uptake. These cells migrate to form bracelet cell arrangements around the nervous tissues between day 4 to day 10 of embryonic differentiation which lasts 14 days in toto. A number of different kinds of intercellular junction form between the bracelet cells from day 8 to day 13 of development. These include gap junctions with features characteristic of arthropods, which seem to assemble by lateral migration of 13-nm E face intramembranous particles (IMPS), which ultimately cluster to form a large number of mature plaques of varying diameters. Less numerous are tight junctions which serve to restrict entry of exogenous molecules, including lanthanum and cationic ferritin, thereby forming the blood- brain barrier; these appear to assemble by migration of individual 8- to lo-nm P face IMPS into ridges which are found between the overlapping fingers of the perineurial bracelet cell processes. Septate junctions also mature at this stage in embryonic development by apparent assembly of IMPS into characteristic aligned rows; these may serve to slow down the entry of positively charged molecules as well as being adhesive, although anionic ferritin may leak into the CNS even after septate and tight junction formation.
    [Show full text]
  • Hedgehog Promotes Production of Inhibitory Interneurons in Vivo and in Vitro from Pluripotent Stem Cells
    Journal of Developmental Biology Review Hedgehog Promotes Production of Inhibitory Interneurons in Vivo and in Vitro from Pluripotent Stem Cells Nickesha C. Anderson *, Christopher Y. Chen and Laura Grabel Department of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA; [email protected] (C.Y.C.); [email protected] (L.G.) * Correspondence: [email protected]; Tel.: +1-860-778-8898 Academic Editors: Henk Roelink and Simon J. Conway Received: 11 July 2016; Accepted: 17 August 2016; Published: 26 August 2016 Abstract: Loss or damage of cortical inhibitory interneurons characterizes a number of neurological disorders. There is therefore a great deal of interest in learning how to generate these neurons from a pluripotent stem cell source so they can be used for cell replacement therapies or for in vitro drug testing. To design a directed differentiation protocol, a number of groups have used the information gained in the last 15 years detailing the conditions that promote interneuron progenitor differentiation in the ventral telencephalon during embryogenesis. The use of Hedgehog peptides and agonists is featured prominently in these approaches. We review here the data documenting a role for Hedgehog in specifying interneurons in both the embryonic brain during development and in vitro during the directed differentiation of pluripotent stem cells. Keywords: Sonic hedgehog; GABAergic interneurons; medial ganglionic eminence; pluripotent stem cells 1. Introduction Glutamatergic projection neurons and gamma-aminobutyric acid-containing (GABAergic) inhibitory interneurons are the two major classes of neurons in the cerebral cortex. Despite constituting only around 20%–30% of the total neuron population in the mammalian cortex, inhibitory interneurons play a key role in modulating the overall activity of this region [1].
    [Show full text]
  • The Intrinsic Cardiac Nervous System and Its Role in Cardiac Pacemaking and Conduction
    Journal of Cardiovascular Development and Disease Review The Intrinsic Cardiac Nervous System and Its Role in Cardiac Pacemaking and Conduction Laura Fedele * and Thomas Brand * Developmental Dynamics, National Heart and Lung Institute (NHLI), Imperial College, London W12 0NN, UK * Correspondence: [email protected] (L.F.); [email protected] (T.B.); Tel.: +44-(0)-207-594-6531 (L.F.); +44-(0)-207-594-8744 (T.B.) Received: 17 August 2020; Accepted: 20 November 2020; Published: 24 November 2020 Abstract: The cardiac autonomic nervous system (CANS) plays a key role for the regulation of cardiac activity with its dysregulation being involved in various heart diseases, such as cardiac arrhythmias. The CANS comprises the extrinsic and intrinsic innervation of the heart. The intrinsic cardiac nervous system (ICNS) includes the network of the intracardiac ganglia and interconnecting neurons. The cardiac ganglia contribute to the tight modulation of cardiac electrophysiology, working as a local hub integrating the inputs of the extrinsic innervation and the ICNS. A better understanding of the role of the ICNS for the modulation of the cardiac conduction system will be crucial for targeted therapies of various arrhythmias. We describe the embryonic development, anatomy, and physiology of the ICNS. By correlating the topography of the intracardiac neurons with what is known regarding their biophysical and neurochemical properties, we outline their physiological role in the control of pacemaker activity of the sinoatrial and atrioventricular nodes. We conclude by highlighting cardiac disorders with a putative involvement of the ICNS and outline open questions that need to be addressed in order to better understand the physiology and pathophysiology of the ICNS.
    [Show full text]
  • From Nematode Neurons to Vertebrate Neural Crest
    Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press RESEARCH COMMUNICATION types in vertebrate embryos, and thus a potential model Evolutionary conservation for understanding the molecular basis of migratory pro- of cell migration genes: cesses. However, due to the difficulty of visualizing mo- tile cells in living vertebrate embryos, the problem of from nematode neurons neural crest migration has not been particularly ame- to vertebrate neural crest nable to genetic dissection, and only a limited number of genes that affect aspects of neural crest migration have Yun Kee,1,3 Byung Joon Hwang,1,2,3 been identified (Halloran and Berndt 2003). 1,2 The feasibility of genetic screens in invertebrates, Paul W. Sternberg, such as Caenorhabditis elegans and Drosophila melano- 1,4 and Marianne Bronner-Fraser gaster, has allowed the isolation of mutants that disrupt various aspects of cell migration (Garriga and Stern 1994; 1Division of Biology, California Institute of Technology, Montell 1999). For example, C. elegans hermaphrodite- Pasadena, California 91125, USA; 2Howard Hughes Medical specific neurons (HSN) undergo long-range migrations Institute, California Institute of Technology, Pasadena, from their location at birth in the tail to positions flank- California 91125, USA ing the gonadal primordium in the midbody of the ani- Because migratory cells in all animals share common mal (Fig. 1B). Forward genetic screening has identified 15 genes required for HSN migration, including transcrip- properties, we hypothesized that genetic networks in- tion factors, signaling, and adhesion molecules (Garriga volved in cell migration may be conserved between and Stern 1994). nematodes and vertebrates.
    [Show full text]
  • Mutations in Lottchen Cause Cell Fate Transformations in Both Neuroblast and Glioblast Lineages in the Drosophila Embryonic Central Nervous System
    Development 124, 673-681 (1997) 673 Printed in Great Britain © The Company of Biologists Limited 1997 DEV7540 Mutations in lottchen cause cell fate transformations in both neuroblast and glioblast lineages in the Drosophila embryonic central nervous system Marita Buescher and William Chia* Institute of Molecular and Cell Biology, National University of Singapore, Singapore 119260 *Author for correspondence (e-mail: [email protected]) SUMMARY The Drosophila embryonic central nervous system (CNS) distinct GMC4-2a-like cells that do not share the same develops from a stereotyped pattern of neuronal progeni- parental NB, indicating that a second NB has acquired the tor cells called neuroblasts (NB). Each NB has a unique potential to produce a GMC and a neuron which is identity that is defined by the time and position of its normally restricted to the NB4-2 lineage. Moreover, the ltt formation and a characteristic combination of genes it mutations lead to a loss of correctly specified longitudinal expresses. Each NB generates a specific lineage of neurons glia; this coincides with severely defective longitudinal con- and/or glia. Here we describe the genetic and phenotypic nectives. Therefore, lottchen plays a role in specifying the analysis of lottchen (ltt), a novel gene whose loss of function identity of both neuroblast and glioblast lineages in the causes a change in the identity of at least one NB as well as Drosophila embryonic CNS. We discuss the possibility that cell fate transformations within the lateral glioblast lineage. ltt may act to differentiate NB identity along the medial In wildtype embryos the parental NB of the motoneuron lateral axis.
    [Show full text]
  • Blood Vessels As a Scaffold for Neuronal Migration
    Neurochemistry International 126 (2019) 69–73 Contents lists available at ScienceDirect Neurochemistry International journal homepage: www.elsevier.com/locate/neuint Blood vessels as a scaffold for neuronal migration T ∗ Teppei Fujiokaa,b,1, Naoko Kanekoa,1, Kazunobu Sawamotoa,c, a Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, 467-8601, Japan b Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, 467-8601, Japan c Division of Neural Development and Regeneration, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8585, Japan ARTICLE INFO ABSTRACT Keywords: Neurogenesis and angiogenesis share regulatory factors that contribute to the formation of vascular networks Neuronal migration and neuronal circuits in the brain. While crosstalk mechanisms between neural stem cells (NSCs) and the vas- Blood vessel culature have been extensively investigated, recent studies have provided evidence that blood vessels also play Ventricular-subventricular zone an essential role in neuronal migration in the brain during development and regeneration. The mechanisms of Neurogenesis the neuronal migration along blood vessels, referred to as “vascular-guided migration,” are now being eluci- Angiogenesis dated. The vascular endothelial cells secrete soluble factors that attract and promote neuronal migration in Brain regeneration collaboration with astrocytes that enwrap the blood vessels. In addition, especially in the adult brain, the blood vessels serve as a migration scaffold for adult-born immature neurons generated in the ventricular-sub- ventricular zone (V-SVZ), a germinal zone surrounding the lateral ventricles. The V-SVZ-derived immature neurons use the vascular scaffold to assist their migration toward an injured area after ischemic stroke, and contribute to neuronal regeneration.
    [Show full text]
  • Gliogenesis Depends on Glide/Gcm Through Asymmetric Division Of
    Developmental Biology 216, 265–275 (1999) Article ID dbio.1999.9511, available online at http://www.idealibrary.com on View metadata, citation and similar papers at core.ac.uk brought to you by CORE Gliogenesis Depends on glide/gcm through provided by Elsevier - Publisher Connector Asymmetric Division of Neuroglioblasts Roberto Bernardoni, Martial Kammerer, Jean-Luc Vonesch, and Angela Giangrande1 Institut de Ge´ne´tique et Biologie Mole´culaire et Cellulaire, IGBMC/CNRS/INSERM/ULP, BP 163, 67404 Illkirch, c.u. de Strasbourg, France Some neurons and glial cells originate from neuroblasts and glioblasts, stem cells that delaminate from the ectoderm of developing fly embryos. A second class of glial cells and neurons differentiates from multipotent precursors, the neuroglioblasts. The differentiation of both glial cell types depends on glial cell deficient/glial cell missing (glide/gcm). Although it has been shown that this transcription factor promotes gliogenesis at the expense of neurogenesis, the cellular mechanisms underlying this fate choice are poorly understood. Using loss and gain of function glide/gcm mutations here we show that the cell fate choice takes place in the neuroglioblast, which divides and produces a glioblast and a neuroblast. Such choice requires the asymmetric distribution of glide/gcm RNA, which accumulates preferentially on one side of the neuroglioblast and is inherited by one cell, the presumptive glioblast. Interestingly, glial cells can differentiate from cells that delaminate as neuroglioblasts or they can arise from cells that start expressing glide/gcm several hours after delamination of a neuroblast. Altogether, these findings identify a novel type of asymmetric cell division and disclose the lineage relationships between glia and neurons.
    [Show full text]
  • Human Neurospheres: from Stained Sections to Three
    Communication • DOI: 10.2478/s13380-011-0007-4 • Translational Neuroscience • 2(1) • 2011 • 43-48 Translational Neuroscience HUMAN NEUROSPHERES: FROM Emanuela Monni1,2, Terenzio Congiu3, STAINED SECTIONS TO THREE- Denise Massa1, Roxana Nat4,5, DIMENSIONAL ASSEMBLY Andrea Diana1,* Abstract 1Department of Cytomorphology, Human neurospheres are free-floating spherical clusters generated from a single neural stem cell and Laboratory of Neurogenesis and Neuropoiesis, comprising cells at different stages of maturation in the neuronal and glial lineages. Although recent University of Cagliari, Monserrato, findings have disproved the original idea of clonally derived neurospheres according to the paradigm of one 09042, Italy stem cell – one neurosphere, they still represent a valid model for growing neural stem cell cultures in vitro. While the immunocytochemical approach to the identification of stem cells, progenitor cells, and mature 2Laboratory of Neural Stem Cell Biology and cells has been extensively used, scant data are available about the ultrastructural arrangement of different Therapy, University Hospital, cell types within the neurosphere. This paper provides, by means of scanning electron microscopy, some new Lund, SE-221 84 Sweden insights into the three-dimensional assembly of human neurospheres, trying to correlate some parameters 3Department of Human Morphology, such as cell density, shape and growing strategies with the immunolocalization of some antigens such as nestin, GFAP, α-internexin and βIII-tubulin. The major findings
    [Show full text]
  • Ectoderm: Neurulation, Neural Tube, Neural Crest
    4. ECTODERM: NEURULATION, NEURAL TUBE, NEURAL CREST Dr. Taube P. Rothman P&S 12-520 [email protected] 212-305-7930 Recommended Reading: Larsen Human Embryology, 3rd Edition, pp. 85-102, 126-130 Summary: In this lecture, we will first consider the induction of the neural plate and the formation of the neural tube, the rudiment of the central nervous system (CNS). The anterior portion of the neural tube gives rise to the brain, the more caudal portion gives rise to the spinal cord. We will see how the requisite numbers of neural progenitors are generated in the CNS and when these cells become post mitotic. The molecular signals required for their survival and further development will also be discussed. We will then turn our attention to the neural crest, a transient structure that develops at the site where the neural tube and future epidermis meet. After delaminating from the neuraxis, the crest cells migrate via specific pathways to distant targets in an embryo where they express appropriate target-related phenotypes. The progressive restriction of the developmental potential of crest-derived cells will then be considered. Additional topics include formation of the fundamental subdivisions of the CNS and PNS, as well as molecular factors that regulate neural induction and regional distinctions in the nervous system. Learning Objectives: At the conclusion of the lecture you should be able to: 1. Discuss the tissue, cellular, and molecular basis for neural induction and neural tube formation. Be able to provide some examples of neural tube defects caused by perturbation of neural tube closure.
    [Show full text]
  • Neuroblast Migration Along Cellular Substrates in the Developing Porcine Brain
    bioRxiv preprint doi: https://doi.org/10.1101/2021.08.19.456958; this version posted August 19, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Neuroblast migration along cellular substrates in the developing porcine brain Demisha D.L. Porter1,2, Sara N. Henry2, Sadia Ahmed2, and Paul D. Morton2* 1Virginia Tech Graduate Program in Translational Biology, Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA. 2Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA. *Correspondence should be addressed to: Paul Morton, Ph.D. ([email protected]). Abstract In the past decade it has become evident that neuroblasts continue to supply the human cortex with interneurons via unique migratory streams shortly following birth. Due to the size of the human brain, these newborn neurons must migrate long distances through complex cellular landscapes to reach their final locations. This process is poorly understood, largely due to technical difficulties in acquiring and studying neurotypical postmortem human samples along with diverging developmental features of well-studied mouse models. We reasoned that migratory streams of neuroblasts utilize cellular substrates, such as blood vessels, to guide their trek from the subventricular zone to distant cortical targets. Here we evaluate the association between young interneuronal migratory streams and their preferred cellular substrates in gyrencephalic piglets during the developmental equivalent of human birth, infancy, and toddlerhood. 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.19.456958; this version posted August 19, 2021.
    [Show full text]