New Molecular Players in the Development of Callosal Projections

Total Page:16

File Type:pdf, Size:1020Kb

New Molecular Players in the Development of Callosal Projections cells Review New Molecular Players in the Development of Callosal Projections Ray Yueh Ku 1 and Masaaki Torii 1,2,* 1 Center for Neuroscience Research, Children’s Research Institute, Children’s National Hospital, Washington, DC 20010, USA 2 Department of Pediatrics, Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA * Correspondence: [email protected] Abstract: Cortical development in humans is a long and ongoing process that continuously modifies the neural circuitry into adolescence. This is well represented by the dynamic maturation of the corpus callosum, the largest white matter tract in the brain. Callosal projection neurons whose long-range axons form the main component of the corpus callosum are evolved relatively recently with a substantial, disproportionate increase in numbers in humans. Though the anatomy of the corpus callosum and cellular processes in its development have been intensively studied by experts in a variety of fields over several decades, the whole picture of its development, in particular, the molecular controls over the development of callosal projections, still has many missing pieces. This review highlights the most recent progress on the understanding of corpus callosum formation with a special emphasis on the novel molecular players in the development of axonal projections in the corpus callosum. Keywords: corpus callosum; callosal projections; cerebral cortex; development; cortical neurons 1. Introduction—The Corpus Callosum Citation: Ku, R.Y.; Torii, M. New The corpus callosum (CC) is the largest white matter tract that connects two cerebral Molecular Players in the Development hemispheres of placental animals. The communication via approximately two hundred of Callosal Projections. Cells 2021, 10, million callosal axons allows efficient information exchange between the two hemispheres, 29. https://dx.doi.org/10.3390/ coordinating our higher-order motor, sensory, and cognitive tasks [1,2]. The human CC is cells10010029 anatomically divided into several regions that topographically connect two hemispheres: The anterior-most rostrum, genu, body, isthmus, and splenium at the posterior end, Received: 5 December 2020 while the mouse CC is usually divided into three regions: genu, body, and splenium Accepted: 23 December 2020 (Figure1A,B). Along the anterior–posterior axis, the genu and rostrum connect the frontal Published: 26 December 2020 and premotor regions of the cerebral cortex, the body conjoins the motor, somatosensory, and parietal regions, while the splenium links the temporal and occipital cortices on both Publisher’s Note: MDPI stays neu- sides [3–5]. Although the organization of the CC is defined anatomically, corresponding tral with regard to jurisdictional claims functional topography has been found based on imaging studies and studies on patients in published maps and institutional who underwent callosal resection, as well as studies using animal models. For example, affiliations. neuronal signals for the motor function pass through the genu, while somatosensory inputs go through posterior body of CC. Axons in isthmus are in charge of transmitting auditory signals, and visual information via splenium [6,7]. Dorsal and ventral parts of the CC then Copyright: © 2020 by the authors. Li- connect the medial and lateral cortical regions, respectively [8–10] (Figure1C). Different censee MDPI, Basel, Switzerland. This parts of the CC, therefore, consist of axonal projections from different cortical regions. article is an open access article distributed In addition, callosal projections from each cortical region also include axons of cortical under the terms and conditions of the neurons in multiple cortical layers [11–13]. It is estimated that 80% of callosal axons come Creative Commons Attribution (CC BY) from neurons in layer II/III, and 20% are from neurons in layer V in the mature brain [11]. license (https://creativecommons.org/ licenses/by/4.0/). Cells 2021, 10, 29. https://dx.doi.org/10.3390/cells10010029 https://www.mdpi.com/journal/cells Cells 2021, 10, x FOR PEER REVIEW 2 of 18 Cells 2021, 10, 29 2 of 17 FigureFigure 1. 1.The The organization organization of the mouse of the corpus mouse callosum corpus (CC). callosum Dorsal (A ),(CC). midsagittal Dorsal (B), ( andA), coronalmidsagittal (C) views (B of), theand CC. Callosal axon projections from each cortical hemisphere cross the midline and primarily connect with homotopic coronal (C) views of the CC. Callosal axon projections from each cortical hemisphere cross the cortical regions in a topographic manner, by which projections from anterior and posterior cortical regions form anterior midlineand posterior and parts primarily of the CC, connect respectively with (represented homotopic by rainbow cortical colors regions in A and inB). a Callosal topographic projections manner, from the medial by which projectionsand lateral regions from of theanterior cortex formand the posterior dorsal and cortical ventral portions regions of theform CC, anterior respectively and (C). posterior parts of the CC, respectively (represented by rainbow colors in A and B). Callosal projections from the medial With these highly precise neuronal connections, the CC integrates inputs from left and lateral regions of the cortex form the dorsal and ventral portions of the CC, respectively (C). and right sides of the body for central processing and coordinates bimanual motor move- ments [14]. The presence of an intact, functional CC facilitates signal exchange between With these highlythe two precise hemispheres neuronal [15]. The connecti integrityons, and the the efficiency CC integrates of interhemispheric inputs information from left and right sides of theexchange body isfor also central strongly processing correlated with and social-cognitive coordinates functions bimanual [16–18 ].motor As such, move- if the formation of CC is compromised (e.g., agenesis, dysgenesis, or hypoplasia) by genetic ments [14]. The presencemutations of or an prenatal intact, exposure functi toonal environmental CC facilitates insults [19 signal–23], the exchange abnormal CC between leads to the two hemispheresvarious [15]. transientThe integrity and permanent and the symptoms. efficiency These of include interhemispheric impairment in problem information solving, exchange is also stronglydyslexia, correlated ataxia, apraxia, with alien social-cognitive limb, agraphia, paresis, functions and mutism [16,17,18]. [1,24]. Understand-As such, if ing the mechanisms of CC development is therefore critical to maintain the health and the formation of CCwellbeing is compromised of human life. (e.g., agenesis, dysgenesis, or hypoplasia) by genetic mutations or prenatal exposureIn the following to environm sections, weental will first insults review the[19,20,21,22,23], findings on prenatal the development abnormal CC leads to variousof transient callosal projection, and permanen and move ontot symptoms. the less understood These postnatal include processes impairment of callosal in projection development. As this review focuses on the molecular mechanisms underlying problem solving, dyslexia,these events, ataxia, we leave apraxia, out some alien important limb, topics agraphia, on CC development, paresis, and including mutism the [1,24]. Understandingformation the mechanisms of midline glial of structure,CC devel myelination,opment is and therefore activity-dependent critical to refinement, maintain the health and wellbeingand instead of human only present life. informative reviews on these topics. In the following2. Prenatalsections, Development we will first of Callosal review Projections the findings on prenatal development of callosal projection, andThe formationmove onto of the the CC beginsless understood with the projection postnatal of pioneer processes fibers from theof cingulatecallosal projection development.and rostrolateral As this review cortices [focuses25–27] at aroundon the the molecular 12th week ofmechanisms gestation (GW) underlying in humans, followed by formation of the genu [20,28]. The fusion of these different parts of the CC these events, we leavecompletes out some at around important GW14, and topics the CC on expands CC development, as the brain increases including in size the [29 ,30for-]. mation of midline glialThough structure, each region growsmyelinat at differention, and rates, theactivity-dependent overall volume of the CCrefinement, increases rapidly and instead only presentin informative early development reviews (GW19–21), on these and continues topics. to grow at a slower rate until it reaches a plateau at around GW33 [29,31,32]. Our current understanding of prenatal development of the CC at the molecular and 2. Prenatal Developmentcellular levelsof Callosal have mainly Projections come from studies using animal models such as mice, cats, The formation andof the monkeys, CC begins while studies with of the fetal pr specimensojection have of supplied pioneer the fibers anatomical from understanding the cingu- of CC development in humans. Since there are many excellent reviews on the prenatal late and rostrolateraldevelopment cortices [25,26,27] of the CC available at around already the (e.g., 12th [11,33 ,week34]), we of will gestation review this (GW) topic focusing in hu- mans, followed by formationon the latest discoveries.of the genu [20,28]. The fusion of these different parts of the CC completes at around GW14, and the CC expands as the brain increases in
Recommended publications
  • Atrial Septal Defect (ASD) – Disorder of the Heart That Is Present at Birth Involving a Hole in the Wall (Septum) Separating the Two Upper Chambers (Atria)
    Glossary of medical terms (grouped by affected system or organ) Atrial septal defect (ASD) – disorder of the heart that is present at birth involving a hole in the wall (septum) separating the two upper chambers (atria) Ventricular septal defect (VSD) – disorder of the heart that is present at birth involving a hole in the wall (septum) separating the two lower chambers (ventricles) Patent ductus arteriosus (PDA) – failure of the ductus arteriosus, an arterial shunt in fetal life, to close before birth (patent refers to remaining open) Polyvalvular disease – damage or defect to a heart valve (mitral, aortic, tricuspid or pulmonary); mitral and tricuspid valves control the flow of blood between the atria and the ventricles Pulmonary stenosis – narrowing or obstruction to blood flow (stenosis) from the right ventricle to the pulmonary artery Coarctation of aorta – narrowing of the aorta, the large blood vessel that delivers oxygen-rich blood to the body Bicuspid aortic valve - aortic valve separates the lower left chamber (left ventricle) of the heart from the aorta. A bicuspid aortic valve has two flaps (cusps) instead of the usual three. This condition is often present with coarctation of aorta. Mitral valve atresia – mitral valve connects the two chambers on the left side of the heart (atrium and ventricle). In this condition, blood is unable to flow between the two chambers. Hypoplastic aorta (hypoplastic left heart syndrome) – left side of the heart is critically underdeveloped so unable to effectively pump blood to the body and causing the right side of the heart to pump blood to the lungs and body.
    [Show full text]
  • Apparent Atypical Callosal Dysgenesis: Analysis of MR Findings in Six Cases and Their Relationship to Holoprosencephaly
    333 Apparent Atypical Callosal Dysgenesis: Analysis of MR Findings in Six Cases and Their Relationship to Holoprosencephaly A. James Barkovich 1 The MR scans of six pediatric patients with apparent atypical callosal dysgenesis (presence of the dorsal corpus callosum in the absence of a rostral corpus callosum) were critically analyzed and correlated with developmental information in order to assess the anatomic, embryologic, and developmental implications of this unusual anomaly. Four patients had semilobar holoprosencephaly; the dorsal interhemispheric commis­ sure in these four infants resembled a true callosal splenium. All patients in this group had severe developmental delay. The other two patients had complete callosal agenesis with an enlarged hippocampal commissure mimicking a callosal splenium; both were developmentally and neurologically normal. The embryologic implications of the pres­ ence of these atypical interhemispheric connections are discussed. Differentiation between semilobar holoprosencephaly and agenesis of the corpus callosum with enlarged hippocampal commissure-two types of apparent atypical callosal dysgenesis-can be made by obtaining coronal, short TR/TE MR images through the frontal lobes. Such differentiation has critical prognostic implications. AJNR 11:333-339, March{Apri11990 Abnormalities of the corpus callosum are frequently seen in patients with con­ genital brain malformations [1-5); a recent publication [5) reports an incidence of 47%. The corpus callosum normally develops in an anterior to posterior direction. The genu forms first, followed by the body, splenium, and rostrum. Dysgenesis of the corpus callosum is manifested by the presence of the earlier-formed segments (genu , body) and absence of the later-formed segments (splenium, rostrum) [4-6]. We have recently encountered six patients with findings suggestive of atypical callosal dysgenesis in whom there was apparent formation of the callosal splenium in the absence of the genu and body.
    [Show full text]
  • Calcium Ion Distribution in Nascent Pioneer Axons and Coupled Preaxonogenesis Neurons in Situ
    The Journal of Neuroscience, May 1991, 1 I(5): 1300-l 308 Calcium Ion Distribution in Nascent Pioneer Axons and Coupled Preaxonogenesis Neurons in situ David Bentley,’ Peter B. Guthrie,2 and Stanley B. Kater2 ‘Department of Molecular and Cell Biology, University of California, Berkeley, California 94720 and 2Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, Colorado 80523 The “calcium hypothesis” of regulation of growth cone mo- and Lux, 1989). In a variety of cell types, growth cone motility tility and neurite elongation has derived from analysis of a and neurite elongation have been correlated with intracellular variety of neurons growing in vitro. It proposes that calcium calcium concentration (Anglister et al., 1982; Connor, 1986; ion concentration within growth cones is an important reg- Cohan et al., 1987; Goldberg, 1988; Lankford and Letoumeau, ulator of motility and growth. We now extend this analysis 1989; Silver et al., 1989, 1990; Tolkovsky et al., 1990). Inter- by investigating calcium concentrations within growth cones actions with both soluble and substratemolecules influence in- and nascent neurites of identified embryonic neurons grow- tracellular calcium levels. Exposure of growth conesto a variety ing on their normal substrate in situ. of neurotransmitters can arrest or otherwise regulate growth The pair of Til pioneer neurons are the first to extend (Haydon et al., 1984; Connor et al., 1987; Mattson et al., 1988; axons in limb buds of grasshopper embryos. Their growth McCobb and Kater, 1988; McCobb et al., 1988). This effect cones migrate along a stereotyped pathway, where they en- appearsto be mediated, at least in part, by alteration of intra- counter a series of guidance cues, including preaxonoge- cellular calcium levels through voltage-gated calcium channels nesis afferent neurons (guidepost cells).
    [Show full text]
  • Anatomy of the Corpus Callosum Reveals Its Function
    The Journal of Neuroscience, February 13, 2008 • 28(7):1535–1536 • 1535 Journal Club Editor’s Note: These short critical reviews of recent papers in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to summarize the important findings of the paper and provide additional insight and comentary. For more information on the format and purpose of the Journal Club, please see http://www.jneurosci.org/misc/ifa_features.shtml. Anatomy of the Corpus Callosum Reveals Its Function Eric Mooshagian Department of Psychology, University of California, Los Angeles, California 90095-1563 Review of Wahl et al. (http://www.jneurosci.org/cgi/content/full/27/45/12132) The corpus callosum (CC) comprises ax- views of the CC. In contrast, a few recent amining callosal topography, suggesting a ons connecting the cortices of the two ce- studies have used diffusion tensor imag- more posterior crossing of CMFs (for dis- rebral hemispheres and is the principal ing (DTI) methods to re-evaluate callosal cussion, see Wahl et al., 2007). In addi- white matter fiber bundle in the brain. As topography (for discussion, see Wahl et tion, the present study goes beyond a recently as the mid 20th century, the CC al., 2007). These methods challenge the demonstration of topography by reveal- was thought to serve no other purpose conventional partitioning schemes used ing, for the first time, a clear somatotopy than preventing the two hemispheres to divide the CC into functionally signifi- of CMFs; hand fibers were situated ventral from collapsing on one another (Bogen, cant regions (Witelson, 1989). and anterior to foot fibers, and lip fibers, 1979).
    [Show full text]
  • Crossed Optic Ataxia: Possible Role of the Dorsal Splenium
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.46.6.533 on 1 June 1983. Downloaded from Journal of Neurology, Neurosurgery, and Psychiatry 1983;46:533-539 Crossed optic ataxia: possible role of the dorsal splenium JOSE M FERRO,* JM BRAVO-MARQUES,* A CASTRO-CALDAS,* LOBO ANTUNESt From the Language Research Laboratory* and the Neuropathology Laboratory, t Centro de Estudos Egas Moniz (INIC), Department ofNeurology, Hospital de Santa Maria, Lisbon, Portugal SUMMARY An unusual combination of disconnective syndromes is reported: transcortical motor aphasia, left arm apraxia and optic ataxia. Neuropathological examination showed a left parieto-occipital and a subcortical frontal infarct and a lesion of the dorsal part of the posterior two-fifths of the callosum. The frontal lesion caused the transcortical motor aphasia and pro- duced the left arm apraxia. Visuomotor incoordination in the right hemispace was due to the left parieto-occipital infarct, while the crossed optic ataxia in the left hemispace was attributed to the callosal lesion. It is proposed that the pathway that serves crossed visual reaching passes through the dorsal part of the posterior callosum. This case reinforces the growing evidence that fibres in the corpus callosum are arranged in ventro-dorsal functional lamination. Protected by copyright. Optic ataxia or visuomotor ataxia' consists of a dis- Recondo and Dumas', induces a crossed optic turbance in reaching under visual control that may ataxia, that is, inability to reach in one hemifield affect one or both hands, and be present either in with the hand of the opposite side) is, according to the whole or in part of the visual fields.
    [Show full text]
  • Robo1 and Robo2 Control the Development of the Lateral Olfactory Tract
    The Journal of Neuroscience, March 14, 2007 • 27(11):3037–3045 • 3037 Development/Plasticity/Repair Robo1 and Robo2 Control the Development of the Lateral Olfactory Tract Coralie Fouquet,1,2 Thomas Di Meglio,1,2 Le Ma,4 Takahiko Kawasaki,3 Hua Long,4 Tatsumi Hirata,3 Marc Tessier-Lavigne,3 Alain Che´dotal,1,2 and Kim T. Nguyen-Ba-Charvet1,2 1Centre National de la Recherche Scientifique and 2Universite´ Pierre et Marie Curie-Paris 6, Unite´ Mixte de Recherche 7102, Paris, 75005 France, 3Division of Brain Function, National Institute of Genetics, Graduate University for advanced Studies (Sokendai), Yata 1111, Mishima 411-8540, Japan, and 4Howard Hughes Medical Institute, Department of Biological sciences, Stanford University, Stanford, California 94305 The development of olfactory bulb projections that form the lateral olfactory tract (LOT) is still poorly understood. It is known that the septum secretes Slit1 and Slit2 which repel olfactory axons in vitro and that in Slit1Ϫ/Ϫ;Slit2Ϫ/Ϫ mutant mice, the LOT is profoundly disrupted.However,theinvolvementofSlitreceptors,theroundabout(Robo)proteins,inguidingLOTaxonshasnotbeendemonstrated. We show here that both Robo1 and Robo2 receptors are expressed on early developing LOT axons, but that only Robo2 is present at later developmental stages. Olfactory bulb axons from Robo1Ϫ/Ϫ;Robo2Ϫ/Ϫ double-mutant mice are not repelled by Slit in vitro. The LOT develops normally in Robo1Ϫ/Ϫ mice, but is completely disorganized in Robo2Ϫ/Ϫ and Robo1Ϫ/Ϫ;Robo2Ϫ/Ϫ double-mutant embryos, with many LOT axons spreading along the ventral surface of the telencephalon. Finally, the position of lot1-expressing cells, which have been proposed to be the LOT guidepost cells, appears unaffected in Slit1Ϫ/Ϫ;Slit2Ϫ/Ϫ mice and in Robo1Ϫ/Ϫ;Robo2Ϫ/Ϫ mice.
    [Show full text]
  • Mitochondrial Physiology Within Myelinated Axons in Health and Disease : an Energetic Interplay Between Counterparts Gerben Van Hameren
    Mitochondrial physiology within myelinated axons in health and disease : an energetic interplay between counterparts Gerben Van Hameren To cite this version: Gerben Van Hameren. Mitochondrial physiology within myelinated axons in health and disease : an energetic interplay between counterparts. Human health and pathology. Université Montpellier, 2018. English. NNT : 2018MONTT084. tel-02053421 HAL Id: tel-02053421 https://tel.archives-ouvertes.fr/tel-02053421 Submitted on 1 Mar 2019 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. THÈSE POUR OBTENIR LE GRADE DE DOCTEUR DE L’UNIVERSITÉ DE M ONTPELLIER En Biologie Santé École doctorale CBS2 Institut des Neurosciences de Montpellier MITOCHONDRIAL PHYSIOLOGY WITHIN MYELINATED AXONS IN HEALTH AND DISEASE AN ENERGETIC INTERPLAY BETWEEN COUNTERPARTS Présentée par Gerben van Hameren Le 23 Novembre 2018 Sous la direction de Dr. Nicolas Tricaud Devant le jury composé de Prof. Pascale Belenguer, Centre de Recherches sur la Cognition Animale Toulouse Professeur d’université Dr. Guy Lenaers, Mitochondrial Medicine Research Centre Angers Directeur de recherche Dr. Don Mahad, University of Edinburgh Senior clinical lecturer Invité Dr. Marie-Luce Vignais, Institute for Regenerative Medicine & Biotherapy, Montpellier Chargé de recherche 0 Table of contents Prologue .................................................................................................................................................
    [Show full text]
  • Technische Universität München
    TECHNISCHE UNIVERSITÄT MÜNCHEN Lehrstuhl für Entwicklungsgenetik Molecular mechanisms that govern the establishment of sensory-motor networks Rosa-Eva Hüttl Vollständiger Abdruck der von der Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr. E. Grill Prüfer der Dissertation: 1. Univ.-Prof. Dr. W. Wurst 2. Univ.-Prof. Dr. H. Luksch Die Dissertation wurde am 08.12.2011 bei der Technischen Universität München eingereicht und durch die Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt am 27.02.2012 angenommen. Erklärung Hiermit erkläre ich an Eides statt, dass ich die der Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt der Technischen Universität München zur Promotionsprüfung vorgelegte Arbeit mit dem Titel „Molecular mechanisms that govern the establishment of sensory-motor networks“ am Lehrstuhl für Entwicklungsgenetik unter der Anleitung und Betreuung durch Univ.-Prof. Dr. Wolfgang Wurst ohne sonstige Hilfe erstellt und bei der Abfassung nur die gemäß § 6 Abs. 5 angegebenen Hilfsmittel benutzt habe. Ich habe keine Organisation eingeschaltet, die gegen Entgelt Betreuerinnen und Betreuer für die Anfertigung von Dissertationen sucht, oder die mir obliegenden Pflichten hinsichtlich der Prüfungsleistung für mich ganz oder teilweise erledigt. Ich habe die Dissertation in dieser oder
    [Show full text]
  • Pioneer Growth Cone Morphologies Reveal Proximal Increases in Substrate Affinity Within Leg Segments of Grasshopper Embryos
    The Journal of Neuroscience February 1986, 6(2): 364-379 Pioneer Growth Cone Morphologies Reveal Proximal Increases in Substrate Affinity Within Leg Segments of Grasshopper Embryos Michael Gaudy* and David Bentley-f *Biophysics Group and tDepartment of Zoology, University of California, Berkeley, California 94720 We have compared the morphologies of approximately 5000 limb segment boundaries (Bentley and Caudy, 1983b) and antibody-labeled afferent pioneer growth cones fixed at various guidepost cells. The dominant mechanism appears to be the stages of growth along their characteristic path over the epithe- guidepost cells, a set of nonadjacent, axonless cell bodies of lium in the legs of grasshopper embryos, and have used growth immature neurons (Bentley and Caudy, 1983a, b; Bentley and cone morphology as an indicator of differences in the affinity of Keshishian, 1982a, b; Ho and Goodman, 1982; Keshishian and the epithelial substrate for pioneer growth cones in viva. Growth Bentley, 1983a-c; Taghert et al., 1982). Ablation of the most cone morphologies differ markedly between different locations proximal guidepost cell pair has been shown to result in lack of in limb buds, and also in the same location in limbs at different normal growth (Bentley and Caudy, 1983a, b). stages of differentiation. Growth cones characteristically extend Additional mechanisms apparently guide the Ti 1 growth cones branches and lamellae circumferentially along segment bound- proximally before they contact any of the above cues (Bentley aries, and filopodia and lamellae are retained (or extended) and Caudy, 1983b). One possible external cue is an adhesion longer there. Where they contact a relatively well-differentiated gradient on the epithelial substrate over which the pioneer growth segment boundary, the growth cones also abruptly reorient cir- cones navigate (Bentley and Caudy, 1983b; Berlot and Good- cumferentially.
    [Show full text]
  • The Cell Biology of Neuronal Navigation
    review The cell biology of neuronal navigation Hong-jun Song* and Mu-ming Poo† * Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA; e-mail: [email protected] † Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA; e-mail: [email protected] Morphogenesis of the nervous system requires the directed migration of postmitotic neurons to designated locations in the nervous system and the guidance of axon growth cones to their synaptic targets. Evidence suggests that both forms of navigation depend on common guidance molecules, surface receptors and signal transduction pathways that link receptor activation to cytoskeletal reorganization. Future challenges remain not only in identifying all the components of the signalling pathways, but also in understanding how these pathways achieve signal amplification and adaptation—two essential cellular processes for neuronal navigation. euronal navigation during early development is essential for face adhesion molecules have been shown to be important in neu- establishing the highly ordered cellular organization and spe- ronal navigation14. For example, axonal growth along ‘pioneering’ Ncific nerve connections in the nervous system1,2. In the devel- axons, ‘guidepost’ cells, or ‘labelled’ pathways in the developing oping nervous system, newly generated cortical neurons in the ven- embryos15,16 can be attributed to selective adhesion owing to the tricular zone migrate along the surface of radial glia fibres and set- presence of specific cell-adhesion molecules (CAMs) on the neu- tle in the cortical plate to form orderly layers of the cortex3,4. ronal surface14. The migration of postmitotic cortical neurons Neurons generated in subcortical structures also undergo long- along radial glia depends on the presence of specific neuronal sur- range tangential migration to the cortex to form dispersed popula- face proteins, such as astrotactin17 and integrins18,19.
    [Show full text]
  • A Pan-Mammalian Map of Interhemispheric Brain Connections Predates the Evolution of the Corpus Callosum
    A pan-mammalian map of interhemispheric brain connections predates the evolution of the corpus callosum Rodrigo Suáreza,1, Annalisa Paolinoa, Laura R. Fenlona, Laura R. Morcoma, Peter Kozulina, Nyoman D. Kurniawanb, and Linda J. Richardsa,c,1 aQueensland Brain Institute, The University of Queensland, Brisbane, QLD 4070, Australia; bCentre for Advanced Imaging, The University of Queensland, Brisbane, QLD 4070, Australia; and cSchool of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4070, Australia Edited by Jon H. Kaas, Vanderbilt University, Nashville, TN, and approved August 1, 2018 (received for review May 14, 2018) The brain of mammals differs from that of all other vertebrates, in embryonic astroglia (13), which is exclusively present in euthe- having a six-layered neocortex that is extensively interconnected rians (14). The evolution of the corpus callosum as a distinct within and between hemispheres. Interhemispheric connections are tract allowed a significant expansion of the number of inter- conveyed through the anterior commissure in egg-laying mono- hemispheric neocortical connections in species with large brains tremes and marsupials, whereas eutherians evolved a separate (15). The corpus callosum carries fibers topographically arranged commissural tract, the corpus callosum. Although the pattern of according to the position of their cell bodies (16–18) and con- interhemispheric connectivity via the corpus callosum is broadly nects mostly similar (homotopic) but also different (heterotopic) shared across eutherian species, it is not known whether this pattern regions in each hemisphere (Fig. 1B). However, although the arose as a consequence of callosal evolution or instead corresponds map of callosal fibers in eutherians is well-established, and in- to a more ancient feature of mammalian brain organization.
    [Show full text]
  • Structure and Emergence of Specific Olfactory Glomeruli in The
    The Journal of Neuroscience, December 15, 2001, 21(24):9713–9723 Structure and Emergence of Specific Olfactory Glomeruli in the Mouse Steve M. Potter,1 Chen Zheng,2 David S. Koos,1 Paul Feinstein,2 Scott E. Fraser,1 and Peter Mombaerts2 1Biological Imaging Center, Division of Biology, California Institute of Technology, Pasadena, California 91125, and 2The Rockefeller University, New York, New York 10021 Olfactory sensory neurons (OSNs) expressing a given odorant of mature glomeruli receiving axonal input from OR-expressing receptor (OR) gene project their axons to a few specific glo- OSNs and of the pathways taken by the axons to those glo- meruli that reside at recognizable locations in the olfactory meruli. We also observe that axons of OR-expressing OSNs do bulb. Connecting ϳ1000 populations of OSNs to the ϳ1800 not innervate nearby glomeruli in mature mice. Postnatally, a glomeruli of the mouse bulb poses a formidable wiring problem. tangle of axons from M72-expressing OSNs occupies a large Additional progress in understanding the mechanisms of neu- surface area of the bulb and coalesces abruptly into a proto- ronal connectivity is dependent on knowing how these axonal glomerulus at a reproducible stage of development. These pathways are organized and how they form during develop- results differ in several aspects from those reported for the ment. Here we have applied a genetic approach to this prob- development of glomeruli receiving input from OSNs express- lem. We have constructed by gene targeting novel strains of ing the P2 OR, suggesting the need for a more systematic mice in which either all OSNs or those that express a specific examination of OR-specific glomeruli.
    [Show full text]