Transcriptional Control of Hypothalamic Tanycyte

Total Page:16

File Type:pdf, Size:1020Kb

Transcriptional Control of Hypothalamic Tanycyte TRANSCRIPTIONAL CONTROL OF HYPOTHALAMIC TANYCYTE DEVELOPMENT By Ana Lucia Miranda-Angulo A dissertation submitted to the Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland March 2013 © 2013 Ana Lucia Miranda-Angulo All Rights Reserved Abstract The wall of the ventral third ventricle is composed of two distinct cell populations; tanycytes and ependymal cells. Tanycytes support several hypothalamic functions but little is known about the transcriptional network which regulates their development. We explored the developmental expression of multiple transcription factors by in situ hybridization and found that the retina and anterior neural fold homeobox transcription factor (Rax) was expressed in both ventricular progenitors of the hypothalamic primordium and differentiating tanycytes. Rax is known to participate in retina and hypothalamus development but nothing is known about its function in tanycytes. To explore the role of Rax in hypothalamic tanycyte development we generated Rax haploinsufficient mice. These mice appeared grossly normal, but careful examination revealed a thinning of the third ventricular wall and reduction of tanycyte and ependymal markers. These experiments show that Rax is required for tanycyte and ependymal cell progenitor proliferation and/or survival. Rax haploinsufficiency also resulted in ectopic presence of ependymal cells in the α2 tanycytic zone were few ependymal cells are normally found. Thus, the presence of ependymal cell in this zone suggests that Rax was required for α2 tanycyte differentiation. These changes in the ventricular wall were associated with reduced diffusion of Evans Blue tracer from the ventricle to the hypothalamic parenchyma. Furthermore, we have provided in vivo and in vitro evidence suggesting that RAX protein is secreted by tanycytes, and subsequently internalized by adjacent and distal cells. Finally, we generated an inducible Rax:CreERT2 mouse line which we have found to be selectively active in hypothalamic tanycytes, and will be a useful tool for manipulating gene function in these cells. In conclusion, we ii have provided evidence that during development Rax is necessary to control tanycyte and ependymal cell progenitor proliferation and for α2 tanycyte differentiation. We also show that RAX protein is secreted from tanycytes and internalized by proximal and distal cells. Finally, the inducible Rax:CreERT2/+ mouse line generated in this study will provide an invaluable tool for future studies of tanycyte development and function. Thesis advisor: Seth Blackshaw, Ph.D. Reader: Adam Kaplin M.D, Ph.D. iii Acknowledgements I would like to thank my advisor Seth Blackshaw for his guidance, understanding and support over the past seven years. Seth´s passion for science has always been an inspiration. His enthusiasm for discovering new things and for accomplishing complex projects always challenged me beyond what I thought I could do both personally and scientifically. He gave me enough freedom to think for myself, solve problems and generate new ideas while at the same time being supportive and providing needed guidance. I thank him for believing that I could always accomplish more. I also want to thank all the current and previous members of Seth´s lab who I had the opportunity to interact with. They made my days much better and the challenges easier. I especially want to thank Mardi Byerly, a previous postdoc in Seth´s lab, who helped me during some of the hardest times. She not only encouraged me but also spent many hours helping me with critical experiments even when she was exhausted. I want to thank Jimmy de Melo for his discussions about science and life, and for letting me use his critical eye and experience. He was encouraging and supportive at difficult times and did not hesitate to listen and help. I would like to thank Hong Wang for her dedication, efficiency, and patience when performing all my genotyping and lab ordering. Her assistance made many of my experiments possible. I would like to thank Thomas Pak for his dedication and efforts to make the functional characterization of our knock-in mice possible. I also would like to thank Lizhi, our previous technician and a good friend. She was always willing to make probes or anything else I needed. Her smile and willingness to work were inspiring. I thank Janny, a rotating undergrad, who was a great companion during the last months of my graduate training and who helped me with image analysis. I iv thank Thuzar and Liz for their gracious ways and ability to create a friendly lab environment. I also would like to thank them for giving me a very nice photo album that will never let me forget the people I met during this period of my life. Thanks to Juan for letting me speak Spanish to him in the lab to feel a little closer to my home country, and Kai for sharing his enthusiasm and curiosity for science which reminded me how much fun science can be. I want to thank Dan, who joined Seth’s lab at the same time than I did. Together we accepted the challenge of studying tanycytes for the first time in this lab, his findings and technical expertise were very helpful for the development of my experiments. Thanks to Erin, Eric, and E.J. for their positiveness and friendship at all times. I would also like to thank Nicole and Aki, the first two members of Seth’s lab, who welcomed me and guided me during my first years of training. I want to thank Vani, a former undergrad in the lab. She helped start our great adventure studying tanycytes in Seth’s lab. I want to thank all the people from other labs in the neuroscience department at Johns Hopkins who helped me with advice and/or reagents, especially Caitlin Engelhard, a previous member of David Ginty’s lab. Caitlin kindly and patiently walked me through the generation of the knock-in constructs. I would also like to thank Shin Kang, a previous member of Dwight Bergles lab. He gave me helpful advice and contributed reagents for the generation of the knock-in constructs. Many thanks to Michelle Pucak for her guidance with experiments and valuable help with the Imaris software and to Claudia Ruiz, a neuroscience graduate student who rotated in our lab and made possible to obtain data necessary to start the knock-in mouse project. v People from Hopkins facilities were indispensable to me during my graduate studies. I want to give a special thanks to Barbara, Mike, Loza, Scot and Ester from the Microscope Core Facility for their hospitality, friendliness, and willingness to assist me in every step of imaging and analysis. I also thank Chip and Holly from the Johns Hopkins transgenic core. They made possible the generation of the knock-in mice. Also, thanks to the people in the mouse facility who took great care of my mice. I want to specially thank the members of my thesis committee: David Ginty, Nicholas Gaiano, Hongjun Song, and Adam Kaplin; for their guidance not only in the academic area, but also during personal difficulties. They were all very helpful in pushing me to accomplish my goals. I want to thank Beth and Rita, as well as other administrative members who helped make possible the existence of this wonderful graduate program, and for making me feel as an important member of the neuroscience department family. I thank my previous advisors during my postdoctoral fellowship at NIMH. Dr. Cynthia Weickert and Daniel Weinberger were both great mentors and gave me a great deal of support and allowed me to be able to move toward my graduate training at Hopkins. I want to thank the PAHO and NIH for giving me the opportunity to obtain my postdoctoral training at NIMH and for their financial support. Also, I thank the Universidad de Antioquia in Colombia for its financial support during all my training in the United States. I especially thank Dr. Carlos Palacio, the vice dean of the Universidad de Antioquia, who helped me solve all kind administrative difficulties necessary for me to finish my graduate training. vi I thank all our collaborators who donated mice or helped with experiments: Tomomi Shimogori, Jin Woo Kim, Peter Mathers, Gordon Fishell, Xinzhong Dong, and Jeremy Nathans. I want to thank my friends Lindsay, Lauren, Prya, Rob, Heather and Mala who made my time at Hopkins and in Baltimore a happy one. Thanks to all who kindly helped editing this thesis Mardi, Jimmy, Lindsay, Juan, and Wendy. I want to thank my family. My mother, who traveled back and forward from my home county, every year for eight years, to help me taking care of my children which was essential to me during my graduate studies. Without her help I would not have had peace of mind during my long lab hours. I thank my cousin Melisa who entertained my energetic younger son allowing me to write my thesis. I especially want to thank my husband Luis. He was my rock during all the challenging circumstances that arose. He supported and encouraged me and would always be there to remind me that I could achieve my goals and that he would do everything he could to help me make it possible. His positivity and love were essential for me during the most difficult times. I also thank him for being the great father that he is and for making sure the kids had all they needed when I could not be there during my long days in the lab. I thank my son Tomas who most of the time was able to patiently wait for me to be able to spend time with him. Although I stretched his patience to the limit he always gave me a smile and a hug and reminded me that he was there for me and loved me very much.
Recommended publications
  • Vocabulario De Morfoloxía, Anatomía E Citoloxía Veterinaria
    Vocabulario de Morfoloxía, anatomía e citoloxía veterinaria (galego-español-inglés) Servizo de Normalización Lingüística Universidade de Santiago de Compostela COLECCIÓN VOCABULARIOS TEMÁTICOS N.º 4 SERVIZO DE NORMALIZACIÓN LINGÜÍSTICA Vocabulario de Morfoloxía, anatomía e citoloxía veterinaria (galego-español-inglés) 2008 UNIVERSIDADE DE SANTIAGO DE COMPOSTELA VOCABULARIO de morfoloxía, anatomía e citoloxía veterinaria : (galego-español- inglés) / coordinador Xusto A. Rodríguez Río, Servizo de Normalización Lingüística ; autores Matilde Lombardero Fernández ... [et al.]. – Santiago de Compostela : Universidade de Santiago de Compostela, Servizo de Publicacións e Intercambio Científico, 2008. – 369 p. ; 21 cm. – (Vocabularios temáticos ; 4). - D.L. C 2458-2008. – ISBN 978-84-9887-018-3 1.Medicina �������������������������������������������������������������������������veterinaria-Diccionarios�������������������������������������������������. 2.Galego (Lingua)-Glosarios, vocabularios, etc. políglotas. I.Lombardero Fernández, Matilde. II.Rodríguez Rio, Xusto A. coord. III. Universidade de Santiago de Compostela. Servizo de Normalización Lingüística, coord. IV.Universidade de Santiago de Compostela. Servizo de Publicacións e Intercambio Científico, ed. V.Serie. 591.4(038)=699=60=20 Coordinador Xusto A. Rodríguez Río (Área de Terminoloxía. Servizo de Normalización Lingüística. Universidade de Santiago de Compostela) Autoras/res Matilde Lombardero Fernández (doutora en Veterinaria e profesora do Departamento de Anatomía e Produción Animal.
    [Show full text]
  • 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]
  • Tanycytes of the Adult Hypothalamic Third Ventricle Include Distinct Populations of FGF-Responsive Neural Progenitors
    ARTICLE Received 27 Nov 2012 | Accepted 23 May 2013 | Published 27 Jun 2013 DOI: 10.1038/ncomms3049 OPEN a-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors S.C. Robins1,2,*, I. Stewart1,*, D.E McNay3,4,*, V. Taylor5, C. Giachino5, M. Goetz6, J. Ninkovic6, N. Briancon3,7, E. Maratos-Flier3, J.S Flier3,8, M.V Kokoeva2,3 & M. Placzek1 Emerging evidence suggests that new cells, including neurons, can be generated within the adult hypothalamus, suggesting the existence of a local neural stem/progenitor cell niche. Here, we identify a-tanycytes as key components of a hypothalamic niche in the adult mouse. Long-term lineage tracing in vivo using a GLAST::CreERT2 conditional driver indicates that a-tanycytes are self-renewing cells that constitutively give rise to new tanycytes, astrocytes and sparse numbers of neurons. In vitro studies demonstrate that a-tanycytes, but not b-tanycytes or parenchymal cells, are neurospherogenic. Distinct subpopulations of a-tanycytes exist, amongst which only GFAP-positive dorsal a2-tanycytes possess stem-like neurospherogenic activity. Fgf-10 and Fgf-18 are expressed specifically within ventral tanycyte subpopulations; a-tanycytes require fibroblast growth factor signalling to maintain their proliferation ex vivo and elevated fibroblast growth factor levels lead to enhanced proliferation of a-tanycytes in vivo. Our results suggest that a-tanycytes form the critical component of a hypothalamic stem cell niche, and that local fibroblast growth factor signalling governs their proliferation. 1 MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
    [Show full text]
  • The Interplay Between Neurons and Glia in Synapse Development And
    Available online at www.sciencedirect.com ScienceDirect The interplay between neurons and glia in synapse development and plasticity Jeff A Stogsdill and Cagla Eroglu In the brain, the formation of complex neuronal networks and regulate distinct aspects of synaptic development and amenable to experience-dependent remodeling is complicated circuit connectivity. by the diversity of neurons and synapse types. The establishment of a functional brain depends not only on The intricate communication between neurons and glia neurons, but also non-neuronal glial cells. Glia are in and their cooperative roles in synapse formation are now continuous bi-directional communication with neurons to direct coming to light due in large part to advances in genetic the formation and refinement of synaptic connectivity. This and imaging tools. This article will examine the progress article reviews important findings, which uncovered cellular made in our understanding of the role of mammalian and molecular aspects of the neuron–glia cross-talk that perisynaptic glia (astrocytes and microglia) in synapse govern the formation and remodeling of synapses and circuits. development, maturation, and plasticity since the previ- In vivo evidence demonstrating the critical interplay between ous Current Opinion article [1]. An integration of past and neurons and glia will be the major focus. Additional attention new findings of glial control of synapse development and will be given to how aberrant communication between neurons plasticity is tabulated in Box 1. and glia may contribute to neural pathologies. Address Glia control the formation of synaptic circuits Department of Cell Biology, Duke University Medical Center, Durham, In the CNS, glial cells are in tight association with NC 27710, USA synapses in all brain regions [2].
    [Show full text]
  • Endocannabinoids in Body Weight Control
    pharmaceuticals Review Endocannabinoids in Body Weight Control Henrike Horn †, Beatrice Böhme †, Laura Dietrich and Marco Koch * Institute of Anatomy, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; [email protected] (H.H.); [email protected] (B.B.); [email protected] (L.D.) * Correspondence: [email protected]; Tel.: +49-341-97-22047 † These authors contributed equally. Received: 28 April 2018; Accepted: 28 May 2018; Published: 30 May 2018 Abstract: Maintenance of body weight is fundamental to maintain one’s health and to promote longevity. Nevertheless, it appears that the global obesity epidemic is still constantly increasing. Endocannabinoids (eCBs) are lipid messengers that are involved in overall body weight control by interfering with manifold central and peripheral regulatory circuits that orchestrate energy homeostasis. Initially, blocking of eCB signaling by first generation cannabinoid type 1 receptor (CB1) inverse agonists such as rimonabant revealed body weight-reducing effects in laboratory animals and men. Unfortunately, rimonabant also induced severe psychiatric side effects. At this point, it became clear that future cannabinoid research has to decipher more precisely the underlying central and peripheral mechanisms behind eCB-driven control of feeding behavior and whole body energy metabolism. Here, we will summarize the most recent advances in understanding how central eCBs interfere with circuits in the brain that control food intake and
    [Show full text]
  • Differences in Neural Stem Cell Identity and Differentiation Capacity Drive Divergent Regenerative Outcomes in Lizards and Salamanders
    Differences in neural stem cell identity and differentiation capacity drive divergent regenerative outcomes in lizards and salamanders Aaron X. Suna,b,c, Ricardo Londonoa, Megan L. Hudnalla, Rocky S. Tuana,c, and Thomas P. Lozitoa,1 aCenter for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219; bMedical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; and cDepartment of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA 15213 Edited by Robb Krumlauf, Stowers Institute for Medical Research, Kansas City, MO, and approved July 24, 2018 (received for review March 2, 2018) While lizards and salamanders both exhibit the ability to re- lizard tail regenerate (20), and the key to understanding this generate amputated tails, the outcomes achieved by each are unique arrangement of tissues is in identifying the patterning markedly different. Salamanders, such as Ambystoma mexicanum, signals involved. regenerate nearly identical copies of original tails. Regenerated lizard Both lizards and salamanders follow similar mechanisms of tails, however, exhibit important morphological differences compared tail development during embryonic development. The embryonic with originals. Some of these differences concern dorsoventral pat- spinal cord and surrounding structures are formed and patterned terning of regenerated skeletal and spinal cord tissues; regenerated by the neural tube (21, 22). The neural tube exhibits distinct + salamander tail tissues exhibit dorsoventral patterning, while re- domains: roof plate (characterized by expression of Pax7 , BMP- + + + grown lizard tissues do not. Additionally, regenerated lizard tails lack 2 , and Sox10 among others), lateral domain (Pax6 ), and floor + + characteristically roof plate-associated structures, such as dorsal root plate (Shh , FoxA2 ).
    [Show full text]
  • Reaction of Ependymal Cells to Spinal Cord Injury: a Potential Role for Oncostatin Pathway and Microglial Cells
    bioRxiv preprint doi: https://doi.org/10.1101/2021.02.12.428106; this version posted February 13, 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. Reaction of ependymal cells to spinal cord injury: a potential role for oncostatin pathway and microglial cells *1 *1 *1 2 2 1 R. Chevreau ​ , H Ghazale ,​ C Ripoll ,​ C Chalfouh ,​ Q Delarue ,​ A.L. Hemonnot ,​ H 1 ​ 3 ​ 4 ​ 5 ​ *2 ​ *1 ​ Hirbec ,​ S Wahane ,​ F Perrin ,​ H Noristani ,​ N Guerout ,​ JP Hugnot ​ ​ ​ ​ ​ ​ *equal contribution, listed in alphabetic order 1 Université de Montpellier, INSERM CNRS IGF, France ​ 2 Université de Rouen, France ​ 3 Departments of Neurobiology and Neurosurgery, David Geffen School of Medicine, ​ University of California, Los Angeles, Los Angeles CA 90095-1763, USA. 4 University of Montpellier, INSERM MMDN France ​ 5 Shriners Hospitals Pediatric Research Center, NY, USA ​ Abstract Ependymal cells with stem cell properties reside in the adult spinal cord around the central canal. They rapidly activate and proliferate after spinal cord injury, constituting a source of new cells. They produce neurons and glial cells in lower vertebrates but they mainly generate glial cells in mammals. The mechanisms underlying their activation and their glial-biased differentiation in mammals remain ill-defined. This represents an obstacle to control these cells. We addressed this issue using RNA profiling of ependymal cells before and after injury. We found that these cells activate STAT3 and ERK/MAPK signaling during injury and downregulate cilia-associated genes and FOXJ1, a central transcription factor in ciliogenesis.
    [Show full text]
  • Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease
    cells Review Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease Zachary Finkel, Fatima Esteban, Brianna Rodriguez, Tianyue Fu, Xin Ai and Li Cai * Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA; [email protected] (Z.F.); [email protected] (F.E.); [email protected] (B.R.); [email protected] (T.F.); [email protected] (X.A.) * Correspondence: [email protected] Abstract: Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, main- tenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cere- brospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, prolifer- ation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine. Citation: Finkel, Z.; Esteban, F.; Keywords: central nervous system (CNS); ependymal cells; neural stem and progenitor cells (NSPC); Rodriguez, B.; Fu, T.; Ai, X.; Cai, L. NG2+ cells; neurodegenerative diseases; regenerative medicine; retina injury; spinal cord injury Diversity of Adult Neural Stem and (SCI); traumatic brain injury (TBI) Progenitor Cells in Physiology and Disease. Cells 2021, 10, 2045.
    [Show full text]
  • Hypothalamic Fatty Acids and Ketone Bodies Sensing and Role of FAT/CD36 in the Regulation of Food Intake
    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2019 Hypothalamic fatty acids and ketone bodies sensing and role of FAT/CD36 in the regulation of food intake Le Foll, Christelle Abstract: The obesity and type-2 diabetes epidemic is escalating and represents one of the costliest biomedical challenges confronting modern society. Moreover, the increasing consumption of high fat food is often correlated with an increase in body mass index. In people predisposed to be obese or already obese, the impaired ability of the brain to monitor and respond to alterations in fatty acid (FA) metabolism is increasingly recognized as playing a role in the pathophysiological development of these disorders. The brain senses and regulates metabolism using highly specialized nutrient-sensing neurons located mainly in the hypothalamus. The same neurons are able to detect variation in the extracellular levels of glucose, FA and ketone bodies as a way to monitor nutrient availability and to alter its own activity. In addition, glial cells such as astrocytes create major connections to neurons and form a tight relationship to closely regulate nutrient uptake and metabolism. This review will examine the different pathways by which neurons are able to detect free fatty acids (FFA) to alter its activity and how high fat diet (HFD)-astrocytes induced ketone bodies production interplays with neuronal FA sensing. The role of HFD-induced inflammation and how FA modulate the reward system will also be investigated here. DOI: https://doi.org/10.3389/fphys.2019.01036 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-175790 Journal Article Published Version The following work is licensed under a Creative Commons: Attribution 4.0 International (CC BY 4.0) License.
    [Show full text]
  • Wnt/Β-Catenin Signaling Regulates Ependymal Cell Development and Adult Homeostasis
    Wnt/β-catenin signaling regulates ependymal cell development and adult homeostasis Liujing Xinga, Teni Anbarchiana, Jonathan M. Tsaia, Giles W. Plantb, and Roeland Nussea,c,1 aDepartment of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305; bDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305; and cHoward Hughes Medical Institute, Stanford, CA 94305 Contributed by Roeland Nusse, May 22, 2018 (sent for review February 23, 2018; reviewed by Bin Chen and Samuel Pleasure) In the adult mouse spinal cord, the ependymal cell population that precursors and are present before the onset of neurogenesis. surrounds the central canal is thought to be a promising source of They give rise to radial glial cells, which then become the pre- quiescent stem cells to treat spinal cord injury. Relatively little is dominant progenitors during gliogenesis (19, 20). Eventually, known about the cellular origin of ependymal cells during spinal ependymal cells are formed as the ventricle and the ventricular cord development, or the molecular mechanisms that regulate zone retract through the process of obliteration. This process is ependymal cells during adult homeostasis. Using genetic lineage accompanied by terminal differentiation and exit of radial glial tracing based on the Wnt target gene Axin2, we have character- cells from the ventricular zone (18, 19, 21–24). ized Wnt-responsive cells during spinal cord development. Our Compared with our knowledge about ependymal cells in the results revealed that Wnt-responsive progenitor cells are restricted brain, little is known about the cellular origin of spinal cord to the dorsal midline throughout spinal cord development, which ependymal cells.
    [Show full text]
  • Neuron-Satellite Glial Cell Interactions in Sympathetic Nervous System Development
    NEURON-SATELLITE GLIAL CELL INTERACTIONS IN SYMPATHETIC NERVOUS SYSTEM DEVELOPMENT by Erica D. Boehm A dissertation submitted to the Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland July 2020 © 2020 Erica Boehm All rights reserved. ABSTRACT Glial cells play crucial roles in maintaining the stability and structure of the nervous system. Satellite glial cells are a loosely defined population of glial cells that ensheathe neuronal cell bodies, dendrites, and synapses of the peripheral nervous system (Elfvin and Forsman 1978; Pannese 1981). Satellite glial cells are closely juxtaposed to peripheral neurons with only 20nm of space between their membranes (Dixon 1969). This close association suggests a tight coupling between the cells to allow for possible exchange of important nutrients, yet very little is known about satellite glial cell function and development. How neurons and glial cells co-develop to create this tightly knit unit remains undefined, as well as the functional consequences of disrupting these contacts. Satellite glial cells are derived from the same population of cells that give rise to peripheral neurons, but do not begin differentiation and proliferation until neurogenesis has been completed (Hall and Landis 1992). A key signaling pathway involved in glial specification is the Delta/Notch signaling pathway (Tsarovina et al. 2008). However, recent studies also implicate Notch signaling in the maturation of glia through non- canonical Notch ligands such as Delta/Notch-like EGF-related Receptor (DNER) (Eiraku et al. 2005). Interestingly, it has been reported that levels of DNER in sympathetic neurons may be dependent on the target-derived growth factor, nerve growth factor (NGF), and this signal is prominent in sympathetic neurons at the time in which satellite glial cells are developing (Deppmann et al.
    [Show full text]
  • The Fine Structure of Ependyma in the Brain Of
    THE FINE STRUCTURE OF EPENDYMA IN THE BRAIN OF THE RAT M. W. BRIGHTMAN, Ph.D., and S. L. PALAY, M.D. From the Laboratory of Neuroanatomical Sciences, National Institute of Neurological Diseases and Blindness, National Institutes of Health, Bethesda, Maryland. Dr. Palay's present address is Department of Anatomy, Harvard Medical School, Boston ABSTRACT The ciliated ependyma of the rat brain consists of a sheet of epithelial cells, the luminal surface of which is reflected over ciliary shafts and numerous evaginations of irregular di- mensions. The relatively straight lateral portions of the plasmalemma of contiguous cells are fused at discrete sites to form five-layered junctions or zonulae occludentes which obliterate the intercellular space. These fusions occur usually at some distance below the free surface either independently or in continuity with a second intercellular junction, the zonula adhaerens. The luminal junction is usually formed by a zonula adhaerens or, occasionally, by a zonula occludens. The finely granular and filamentous cytoplasm contains supranuclear dense bodies, some of which are probably lysosomes and dense whorls of perinuclear filaments which send fascicles toward the lateral plasmalemma. The apical regions of the cytoplasm contain the basal body complexes of neighboring cilia. These complexes include a striated basal foot and short, non-striated rootlets emanating from the wall of each basal body. The rootlets end in a zone of granules about the proximal region of the basal body, adjacent to which may lie a striated mass of variable shape. All components of the basal body complex of adjacent cilia are independent of each other.
    [Show full text]