NERVOUS SYSTEM هذا الملف لالستزادة واثراء المعلومات Neuropsychiatry Block
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Suppression of DNA Double-Strand Break Formation by DNA Polymerase B in Active DNA Demethylation Is Required for Development of Hippocampal Pyramidal Neurons
9012 • The Journal of Neuroscience, November 18, 2020 • 40(47):9012–9027 Development/Plasticity/Repair Suppression of DNA Double-Strand Break Formation by DNA Polymerase b in Active DNA Demethylation Is Required for Development of Hippocampal Pyramidal Neurons Akiko Uyeda,1 Kohei Onishi,1 Teruyoshi Hirayama,1,2,3 Satoko Hattori,4 Tsuyoshi Miyakawa,4 Takeshi Yagi,1,2 Nobuhiko Yamamoto,1 and Noriyuki Sugo1 1Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan, 2AMED-CREST, Japan Agency for Medical Research and Development, Suita, Osaka 565-0871, Japan, 3Department of Anatomy and Developmental Neurobiology, Tokushima University Graduate School of Medical Sciences, Kuramoto, Tokushima 770-8503, Japan, and 4Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan Genome stability is essential for brain development and function, as de novo mutations during neuronal development cause psychiatric disorders. However, the contribution of DNA repair to genome stability in neurons remains elusive. Here, we demonstrate that the base excision repair protein DNA polymerase b (Polb) is involved in hippocampal pyramidal neuron fl/fl differentiation via a TET-mediated active DNA demethylation during early postnatal stages using Nex-Cre/Polb mice of ei- ther sex, in which forebrain postmitotic excitatory neurons lack Polb expression. Polb deficiency induced extensive DNA dou- ble-strand breaks (DSBs) in hippocampal pyramidal neurons, but not dentate gyrus granule cells, and to a lesser extent in neocortical neurons, during a period in which decreased levels of 5-methylcytosine and 5-hydroxymethylcytosine were observed in genomic DNA. Inhibition of the hydroxylation of 5-methylcytosine by expression of microRNAs miR-29a/b-1 diminished DSB formation. -
Works Neuroembryology
Swarthmore College Works Biology Faculty Works Biology 1-1-2017 Neuroembryology D. Darnell Scott F. Gilbert Swarthmore College, [email protected] Follow this and additional works at: https://works.swarthmore.edu/fac-biology Part of the Biology Commons Let us know how access to these works benefits ouy Recommended Citation D. Darnell and Scott F. Gilbert. (2017). "Neuroembryology". Wiley Interdisciplinary Reviews: Developmental Biology. Volume 6, Issue 1. DOI: 10.1002/wdev.215 https://works.swarthmore.edu/fac-biology/493 This work is brought to you for free by Swarthmore College Libraries' Works. It has been accepted for inclusion in Biology Faculty Works by an authorized administrator of Works. For more information, please contact [email protected]. HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Wiley Interdiscip Manuscript Author Rev Dev Manuscript Author Biol. Author manuscript; available in PMC 2018 January 01. Published in final edited form as: Wiley Interdiscip Rev Dev Biol. 2017 January ; 6(1): . doi:10.1002/wdev.215. Neuroembryology Diana Darnell1 and Scott F. Gilbert2 1University of Arizona College of Medicine 2Swarthmore College and University of Helsinki Abstract How is it that some cells become neurons? And how is it that neurons become organized in the spinal cord and brain to allow us to walk and talk, to see, recall events in our lives, feel pain, keep our balance, and think? The cells that are specified to form the brain and spinal cord are originally located on the outside surface of the embryo. They loop inward to form the neural tube in a process called neurulation. -
The Genetic Basis of Mammalian Neurulation
REVIEWS THE GENETIC BASIS OF MAMMALIAN NEURULATION Andrew J. Copp*, Nicholas D. E. Greene* and Jennifer N. Murdoch‡ More than 80 mutant mouse genes disrupt neurulation and allow an in-depth analysis of the underlying developmental mechanisms. Although many of the genetic mutants have been studied in only rudimentary detail, several molecular pathways can already be identified as crucial for normal neurulation. These include the planar cell-polarity pathway, which is required for the initiation of neural tube closure, and the sonic hedgehog signalling pathway that regulates neural plate bending. Mutant mice also offer an opportunity to unravel the mechanisms by which folic acid prevents neural tube defects, and to develop new therapies for folate-resistant defects. 6 ECTODERM Neurulation is a fundamental event of embryogenesis distinct locations in the brain and spinal cord .By The outer of the three that culminates in the formation of the neural tube, contrast, the mechanisms that underlie the forma- embryonic (germ) layers that which is the precursor of the brain and spinal cord. A tion, elevation and fusion of the neural folds have gives rise to the entire central region of specialized dorsal ECTODERM, the neural plate, remained elusive. nervous system, plus other organs and embryonic develops bilateral neural folds at its junction with sur- An opportunity has now arisen for an incisive analy- structures. face (non-neural) ectoderm. These folds elevate, come sis of neurulation mechanisms using the growing battery into contact (appose) in the midline and fuse to create of genetically targeted and other mutant mouse strains NEURAL CREST the neural tube, which, thereafter, becomes covered by in which NTDs form part of the mutant phenotype7.At A migratory cell population that future epidermal ectoderm. -
Clonal Dispersion During Neural Tube Formation 4097 of Neuromeres
Development 126, 4095-4106 (1999) 4095 Printed in Great Britain © The Company of Biologists Limited 1999 DEV2458 Successive patterns of clonal cell dispersion in relation to neuromeric subdivision in the mouse neuroepithelium Luc Mathis1,*, Johan Sieur1, Octavian Voiculescu2, Patrick Charnay2 and Jean-François Nicolas1,‡ 1Unité de Biologie moléculaire du Développement, Institut Pasteur, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France 2Unité INSERM 368, Ecole Normale Supérieure, 46 rue d’Ulm, 75230 Paris Cedex 05, France *Present address: Beckman Institute (139-74), California Institute of Technology, Pasadena, CA, 91125, USA ‡Author for correspondence (e-mail: [email protected]) Accepted 5 July; published on WWW 23 August 1999 SUMMARY We made use of the laacz procedure of single-cell labelling the AP and DV axis of the neural tube. A similar sequence to visualize clones labelled before neuromere formation, in of AP cell dispersion followed by an arrest of AP cell 12.5-day mouse embryos. This allowed us to deduce two dispersion, a preferential DV cell dispersion and then by a successive phases of cell dispersion in the formation of the coherent neuroepithelial growth, is also observed in the rhombencephalon: an initial anterior-posterior (AP) cell spinal cord and mesencephalon. This demonstrates that a dispersion, followed by an asymmetrical dorsoventral (DV) similar cascade of cell events occurs in these different cell distribution during which AP cell dispersion occurs in domains of the CNS. In the prosencephalon, differences in territories smaller than one rhombomere. We conclude that spatial constraints may explain the variability in the the general arrest of AP cell dispersion precedes the onset orientation of cell clusters. -
Differentiation of the Cerebellum 2463
Development 128, 2461-2469 (2001) 2461 Printed in Great Britain © The Company of Biologists Limited 2001 DEV1660 Inductive signal and tissue responsiveness defining the tectum and the cerebellum Tatsuya Sato, Isato Araki‡ and Harukazu Nakamura* Department of Molecular Neurobiology, Institute of Development, Aging and Cancer, Seiryo-machi 4-1, Aoba-ku, Sendai 980- 8575, Japan ‡Present address: Department of Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany *Author for correspondence (e-mail: [email protected]) Accepted 11 April 2001 SUMMARY The mes/metencephalic boundary (isthmus) has an Fgf8b repressed Otx2 expression, but upregulated Gbx2 and organizing activity for mesencephalon and metencephalon. Irx2 expression in the mesencephalon. As a result, Fgf8b The candidate signaling molecule is Fgf8 whose mRNA is completely changed the fate of the mesencephalic alar plate localized in the region where the cerebellum differentiates. to cerebellum. Quantitative analysis showed that Fgf8b Responding to this signal, the cerebellum differentiates in signal is 100 times stronger than Fgf8a signal. Co- the metencephalon and the tectum differentiates in the transfection of Fgf8b with Otx2 indicates that Otx2 is a key mesencephalon. Based on the assumption that strong Fgf8 molecule in mesencephalic generation. We have shown by signal induces the cerebellum and that the Fgf8b signal is RT-PCR that both Fgf8a and Fgf8b are expressed, Fgf8b stronger than that of Fgf8a, we carried out experiments to expression prevailing in the isthmic region. The results all misexpress Fgf8b and Fgf8a in chick embryos. Fgf8a did not support our working hypothesis that the strong Fgf8 signal affect the expression pattern of Otx2, Gbx2 or Irx2. -
Auditory and Vestibular Systems Objective • to Learn the Functional
Auditory and Vestibular Systems Objective • To learn the functional organization of the auditory and vestibular systems • To understand how one can use changes in auditory function following injury to localize the site of a lesion • To begin to learn the vestibular pathways, as a prelude to studying motor pathways controlling balance in a later lab. Ch 7 Key Figs: 7-1; 7-2; 7-4; 7-5 Clinical Case #2 Hearing loss and dizziness; CC4-1 Self evaluation • Be able to identify all structures listed in key terms and describe briefly their principal functions • Use neuroanatomy on the web to test your understanding ************************************************************************************** List of media F-5 Vestibular efferent connections The first order neurons of the vestibular system are bipolar cells whose cell bodies are located in the vestibular ganglion in the internal ear (NTA Fig. 7-3). The distal processes of these cells contact the receptor hair cells located within the ampulae of the semicircular canals and the utricle and saccule. The central processes of the bipolar cells constitute the vestibular portion of the vestibulocochlear (VIIIth cranial) nerve. Most of these primary vestibular afferents enter the ipsilateral brain stem inferior to the inferior cerebellar peduncle to terminate in the vestibular nuclear complex, which is located in the medulla and caudal pons. The vestibular nuclear complex (NTA Figs, 7-2, 7-3), which lies in the floor of the fourth ventricle, contains four nuclei: 1) the superior vestibular nucleus; 2) the inferior vestibular nucleus; 3) the lateral vestibular nucleus; and 4) the medial vestibular nucleus. Vestibular nuclei give rise to secondary fibers that project to the cerebellum, certain motor cranial nerve nuclei, the reticular formation, all spinal levels, and the thalamus. -
Fate of the Mammalian Cardiac Neural Crest
Development 127, 1607-1616 (2000) 1607 Printed in Great Britain © The Company of Biologists Limited 2000 DEV4300 Fate of the mammalian cardiac neural crest Xiaobing Jiang1,3, David H. Rowitch4,*, Philippe Soriano5, Andrew P. McMahon4 and Henry M. Sucov2,3,‡ Departments of 1Biological Sciences and 2Cell & Neurobiology, 3Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, 2250 Alcazar St., IGM 240, Los Angeles, CA 90033, USA 4Department of Molecular and Cell Biology, Harvard University, 16 Divinity Ave., Cambridge, MA 02138, USA 5Program in Developmental Biology, Division of Basic Sciences, A2-025, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19024, Seattle, WA 98109, USA *Present address: Department of Pediatric Oncology, Dana Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA ‡Author for correspondence (e-mail: [email protected]) Accepted 26 January; published on WWW 21 March 2000 SUMMARY A subpopulation of neural crest termed the cardiac neural of these vessels. Labeled cells populate the crest is required in avian embryos to initiate reorganization aorticopulmonary septum and conotruncal cushions prior of the outflow tract of the developing cardiovascular to and during overt septation of the outflow tract, and system. In mammalian embryos, it has not been previously surround the thymus and thyroid as these organs form. experimentally possible to study the long-term fate of this Neural-crest-derived mesenchymal cells are abundantly population, although there is strong inference that a similar distributed in midgestation (E9.5-12.5), and adult population exists and is perturbed in a number of genetic derivatives of the third, fourth and sixth pharyngeal arch and teratogenic contexts. -
Role of Glucocorticoids in Tuning Hindbrain Stress Integration
The Journal of Neuroscience, November 3, 2010 • 30(44):14907–14914 • 14907 Cellular/Molecular Role of Glucocorticoids in Tuning Hindbrain Stress Integration Rong Zhang ( ),1,3 Ryan Jankord,1 Jonathan N. Flak,1 Matia B. Solomon,1 David A. D’Alessio,1,2 and James P. Herman1 Departments of 1Psychiatry and 2Internal Medicine, University of Cincinnati, Cincinnati, Ohio 45237, and 3Division of Endocrinology, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115 The nucleus of the solitary tract (NTS) is a critical integrative site for coordination of autonomic and endocrine stress responses. Stress-excitatory signals from the NTS are communicated by both catecholaminergic [norepinephrine (NE), epinephrine (E)] and non- catecholaminergic [e.g., glucagon-like peptide-1 (GLP-1)] neurons. Recent studies suggest that outputs of the NE/E and GLP-1 neurons of the NTS are selectively engaged during acute stress. This study was designed to test mechanisms of chronic stress integration in the paraventricular nucleus, focusing on the role of glucocorticoids. Our data indicate that chronic variable stress (CVS) causes downregu- lation of preproglucagon (GLP-1 precursor) mRNA in the NTS and reduction of GLP-1 innervation to the paraventricular nucleus of the hypothalamus. Glucocorticoids were necessary for preproglucagon (PPG) reduction in CVS animals and were sufficient to lower PPG mRNA in otherwise unstressed animals. The data are consistent with a glucocorticoid-mediated withdrawal of GLP-1 in key stress circuits. In contrast, expression of tyrosine hydroxylase mRNA, the rate-limiting enzyme in catecholamine synthesis, was increased by stress in a glucocorticoid-independent manner. These suggest differential roles of ascending catecholamine and GLP-1 systems in chronic stress, with withdrawal of GLP-1 involved in stress adaptation and enhanced NE/E capacity responsible for facilitation of responses to novel stress experiences. -
Anatomically Distinct Patterns of Diffusion MRI Coherence
NeuroImage 79 (2013) 412–422 Contents lists available at SciVerse ScienceDirect NeuroImage journal homepage: www.elsevier.com/locate/ynimg Radial and tangential neuronal migration pathways in the human fetal brain: Anatomically distinct patterns of diffusion MRI coherence James Kolasinski a,c,1, Emi Takahashi a,b,⁎,1, Allison A. Stevens a, Thomas Benner a, Bruce Fischl a, Lilla Zöllei a,b,2, P. Ellen Grant a,b,2 a Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02119, USA b Division of Newborn Medicine, Department of Medicine/Fetal–Neonatal Neuroimaging and Developmental Science Center, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA c Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK article info abstract Article history: Corticogenesis is underpinned by a complex process of subcortical neuroproliferation, followed by highly orches- Accepted 29 April 2013 trated cellular migration. A greater appreciation of the processes involved in human fetal corticogenesis is vital to Available online 11 May 2013 gaining an understanding of how developmental disturbances originating in gestation could establish a variety of complex neuropathology manifesting in childhood, or even in adult life. Magnetic resonance imaging modalities offer a unique insight into anatomical structure, and increasingly infer information regarding underlying microstructure in the human brain. In this study we applied a combination of high-resolution structural and diffusion-weighted magnetic resonance imaging to a unique cohort of three post-mortem fetal brain specimens, aged between 19 and 22 post-conceptual weeks. -
Heterogeneity in Ventricular Zone Neural Precursors Contributes to Neuronal Fate Diversity in the Postnatal Neocortex
7028 • The Journal of Neuroscience, May 19, 2010 • 30(20):7028–7036 Development/Plasticity/Repair Heterogeneity in Ventricular Zone Neural Precursors Contributes to Neuronal Fate Diversity in the Postnatal Neocortex Elizabeth K. Stancik,1 Ivan Navarro-Quiroga,1 Robert Sellke,2 and Tarik F. Haydar1 1Center for Neuroscience Research, Children’s National Medical Center, Washington, DC 20010, and 2University of Maryland School of Medicine, Baltimore, Maryland 21201 The recent discovery of short neural precursors (SNPs) in the murine neocortical ventricular zone (VZ) challenges the widely held view that radial glial cells (RGCs) are the sole occupants of this germinal compartment and suggests that precursor variety is an important factor of brain development. Here, we use in utero electroporation and genetic fate mapping to show that SNPs and RGCs cohabit the VZ but display different cell cycle kinetics and generate phenotypically different progeny. In addition, we find that RGC progeny undergo additional rounds of cell division as intermediate progenitor cells (IPCs), whereas SNP progeny generally produce postmitotic neurons directly from the VZ. By clearly defining SNPs as bona fide VZ residents, separate from both RGCs and IPCs, and uncovering their unique proliferativeandlineageproperties,theseresultsdemonstratehowindividualneuralprecursorgroupsintheembryonicrodentVZcreate diversity in the overlying neocortex. Introduction progenitors properly form the cerebral cortex as well as for elu- The ventricular zone (VZ) of the dorsal telencephalon contains cidating possible mechanisms of species-specific diversity. the progenitor cells that produce all of the various excitatory In addition to the neural precursors in the VZ, a separate class neurons of the mature neocortex. This process occurs during of neuronal progenitors has been described in the overlying sub- prenatal mammalian brain development through a precisely reg- ventricular zone (SVZ). -
Development and Evolution of the Human Neocortex
Leading Edge Review Development and Evolution of the Human Neocortex Jan H. Lui,1,2,3 David V. Hansen,1,2,4 and Arnold R. Kriegstein1,2,* 1Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA 2Department of Neurology 3Biomedical Sciences Graduate Program University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA 4Present address: Department of Neuroscience, Genentech, Inc., 1 DNA Way, MS 230B, South San Francisco, CA 94080, USA *Correspondence: [email protected] DOI 10.1016/j.cell.2011.06.030 The size and surface area of the mammalian brain are thought to be critical determinants of intel- lectual ability. Recent studies show that development of the gyrated human neocortex involves a lineage of neural stem and transit-amplifying cells that forms the outer subventricular zone (OSVZ), a proliferative region outside the ventricular epithelium. We discuss how proliferation of cells within the OSVZ expands the neocortex by increasing neuron number and modifying the trajectory of migrating neurons. Relating these features to other mammalian species and known molecular regulators of the mouse neocortex suggests how this developmental process could have emerged in evolution. Introduction marsupials begin to reveal how differences in neural progenitor Evolution of the neocortex in mammals is considered to be a key cell populations can result in neocortices of variable size and advance that enabled higher cognitive function. However, neo- shape. Increases in neocortical volume and surface area, partic- cortices of different mammalian species vary widely in shape, ularly in the human, are related to the expansion of progenitor size, and neuron number (reviewed by Herculano-Houzel, 2009). -
Mechanisms of Neurulation: Traditional Viewpoint and Recent Advances
Development 109, 243-270 (L990) Review Article 243 Printed in Great Britain ©The Company of Biologists Limited 1990 Mechanisms of neurulation: traditional viewpoint and recent advances GARY C. SCHOENWOLF* and JODI L. SMITH Department of Anatomy, University of Utah, School of Medicine, Salt Lake City, Utah 84132, USA * Author for correspondence Introduction 243 Traditional viewpoint 248 The three fundamentals of the traditional viewpoint 248 Contemporary viewpoint 248 Regional differences in neural plate shaping and bending 248 Contemporary viewpoint: First fundamental 252 Traditional disregard for extrinsic forces in neurulation 252 Evidence of intrinsic forces in neural plate shaping and extrinsic forces in bending 254 Contemporary viewpoint: Second fundamental 254 Role of neurepithelial cell elongation in neural plate shaping 255 Roles of other form-shaping events in neural plate shaping 255 Cell rearrangement 255 Cell division 256 Role of neurepithelial cell wedging in neural plate bending 257 MHP cell wedging: an active event 259 MHP cell wedging and neural plate furrowing 259 Roles of other form-shaping events in neural plate bending 260 Longitudinal stretching 260 Hinge point formation 262 Expansion of deep tissues 263 Contemporary viewpoint: Third fundamental 264 Role of microtubules in neurepithelial cell elongation 264 Role of apical microfilament bands in neurepithelial cell wedging 264 Role of cell cycle alteration and basal expansion in neurepithelial cell wedging 265 Conclusions 267 Summary In this review article, the traditional