DOCSLIB.ORG

The Involvement of Cell Death and Survival in Neural Tube Defects: a Distinct Role for Apoptosis and Autophagy?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Involvement of Cell Death and Survival in Neural Tube Defects: a Distinct Role for Apoptosis and Autophagy? Cell Death and Differentiation (2008) 15, 1170–1177 & 2008 Nature Publishing Group All rights reserved 1350-9047/08 $30.00 www.nature.com/cdd Review The involvement of cell death and survival in neural tube defects: a distinct role for apoptosis and autophagy? F Cecconi*,1,2, M Piacentini3,4 and GM Fimia3 Neural tube defects (NTDs), such as spina bifida (SB) or exencephaly, are common congenital malformations leading to infant mortality or severe disability. The etiology of NTDs is multifactorial with a strong genetic component. More than 70 NTD mouse models have been reported, suggesting the involvement of distinct pathogenetic mechanisms, including faulty cell death regulation. In this review, we focus on the contribution of functional genomics in elucidating the role of apoptosis and autophagy genes in neurodevelopment. On the basis of compared phenotypical analysis, here we discuss the relative importance of a tuned control of both apoptosome-mediated cell death and basal autophagy for regulating the correct morphogenesis and cell number in developing central nervous system (CNS). The pharmacological modulation of genes involved in these processes may thus represent a novel strategy for interfering with the occurrence of NTDs Cell Death and Differentiation (2008) 15, 1170–1177; doi:10.1038/cdd.2008.64; published online 2 May 2008 Neural tube defects (NTDs) are common (1 in 1000 by participating in folding, pinching off and fusion of neural pregnancies) congenital malformations in humans leading to walls, in neural precursor selection and in postmitotic infant mortality or severe disability. NTD results from failure of competition of neurons for their cellular targets (reviewed in complete neurulation during the fourth week of embryo- De Zio et al.,18Hidalgo and ffrench-Constant,19 Kuan et al.,20 genesis. The etiology of NTDs is complex, with both and Nicotera21). Notably, the main phenotype, which is environmental and genetic contributions.1 In particular, a induced by disruption of apoptosis-related genes regards strong genetic component, accounting for at least 30% of the developing nervous system (see Table 1). Autophagy, an NTDs, has been demonstrated, although only few of the important mechanism for degrading long-lived proteins and genes involved have been structurally and functionally the only known cellular pathway for degrading organelles, has characterized.2 This is mainly due to the fact that neurulation been originally linked to the occurrence of pathological is a complex multistep process involving precise temporal and conditions in the nervous system associated with alternative spatial regulation of gene expression.3–6 Animal models are cell death morphotypes.43–45 Recently, autophagy has been providing insight into the mechanisms participating in correct recognized as a survival process46 and as a key player in neurulation or in its failure.7–9 More than 70 mouse models vertebrate neurodevelopment;47 also, a complex interplay exhibiting NTDs have been described.10–13 Mutations display between autophagy and apoptosis has emerged (reviewed in wide locus heterogeneity, and for many of them, the Ferraro and Cecconi48 and Maiuri et al.49). Interestingly, corresponding human homolog has been found.14,15 These comparative analysis of the phenotypes exhibited by mouse studies suggest the involvement of distinct molecular path- models’ defective in apoptosis or autophagy genes show ways in NTD pathogenesis, ranging from dysregulation of several similitaries, although molecular analysis revealed that homocysteine/folate metabolism to defective cell proliferation they are accounted for by distinct roles at different develop- or death, to disruption of cytoskeleton and migratory mental stages. The data we discuss here suggest that, capabilities and to faulty pyrimidine synthesis.8,9,16,17 Among whereas apoptosis is the main mechanism by which these, special attention is being devoted to apoptosis. mammals can prevent the survival of excess cells in the Apoptosis plays an important role in the morphogenesis and developing nervous system, autophagy regulation may have a homeostasis of the developing central nervous system (CNS) crucial role in the ontogenesis of CNS through a mechanism 1Department of Biology, Dulbecco Telethon Institute, University of Rome ‘Tor Vergata’, Rome 00133, Italy; 2Laboratory of Molecular Neuroembryology, IRCCS Fondazione Santa Lucia, Rome 00143, Italy; 3Laboratory of Cell Biology, National Institute for Infectious Diseases IRCCS ‘L. Spallanzani’, Rome 00149, Italy and 4Department of Biology, University of Rome ‘Tor Vergata’, Rome 00133, Italy *Corresponding author: F Cecconi, Department of Biology, University of Rome Tor Vergata, via della Ricerca Scientifica, Rome 00133, Italy. Tel: þ 390672594230; Fax: þ 39062023500; E-mail: [email protected] Keywords: Ambra1; Apaf1; apoptosome; autophagosome; neurogenesis; neural precursor cells Abbreviations: Ambra1, activating molecule in Beclin 1-regulated autophagy; ATG, autophagy-related gene; CNS, central nervous system; E, embryonic day; IP3, myo-inositol-1,4,5-triphosphate; Lamp, lysosome-associated membrane protein; NPC, neuronal precursor cell; NTDs, neural tube defects; PI3K, phosphatidyl Inositol 3-kinase; SB, spina bifida; TUNEL, terminal uridine deoxynucleotidyl transferase dUTP nick end labeling Received 04.3.08; revised 31.3.08; accepted 31.3.08; Edited by G Melino; published online 02.5.08 Cell death and survival in NTDs F Cecconi et al 1171 Table 1 Neurodevelopmental aspect of phenotypes from the apoptosis or autophagy knockout mice Gene Neurodevelopmental phenotype Reference BaxÀ/À Apoptosis reduction in postmitotic spinal cord motor neurons and 22,23 sympathetic neurons in the PNS À/À À/À 24 Bcl-XL /Bax Massive apoptosis reduction in postmitotic neurons BaxÀ/À/BakÀ/À Accumulation of excess cells within CNS 25 Caspase 3À/À Pronounced effects on the development of the CNS and premature lethality; 26–28 diffuse hyperplasia, ectopic cell masses, abnormal structural organization and augmented number of neurons in several brain areas Caspase 9À/À Excess cells in most CNS regions, brain hyperplasia and exencephaly 29,27 À/À À/À 30 Bcl-XL /Caspase 3 Supernumerary neuronal precursor cells and compensative effect in young postmitotic neurons À/À À/À 31 Bcl-XL /Caspase 9 Neuronal phenotype identical to that of mice lacking only caspase 9; compensative effect in young postmitotic neurons Apaf1À/À Open brain (and/or spina bifida) and forebrain overgrowth; retinal 32,33 overgrowth; delayed cortical layering and enlargement of the mantle layer in the brain; thickening of the hindbrain walls À/À À/À À/À 34 Bcl-XL /Apaf1 Phenotype very similar to Apaf1 , but the Apaf1 deficiency counters the increased apoptosis of postmitotic immature neurons caused by Bcl-XL deficiency Atg5F/F:nestin-Cre (neurons) Progressive neurodegeneration associated with ubiquitinated protein 35 aggregates and inclusion bodies Beclin 1À/À Early defects in ectoderm formation and early embryonic lethality (before 36,37 neural plate determination) Ambra1À/À Decreased autophagy, increased apoptosis, and increased cell proliferation 38 in fetal brain. Neural tube defects and embryonic death Lamp1/Lamp2 Foreshortening of the forebrain 39 Combined or conditional mutations are also included35,39,40–42 involving the need for cell ‘renovation’ in differentiation and encephalon and the central canal of the spinal cord. The cell cycle control rather than for cell demise. anterior portion of the neural tube is then divided into three distinct, interconnected rounded cavities, which distinguish the portion that will become the encephalon, whereas the The Basis of Neural Development in Vertebrates middle and caudal portions remain as a tube and will become The development of vertebrates from the zygote follows a the spinal cord. The most anterior cavity is called the forebrain specific sequence of events: (i) division of the zygote into or prosencephalon, the second is the midbrain or mesence- undifferentiated blastula cells, (ii) formation of three progenitor phalon and finally the most posterior one is the hindbrain or cell layers in a gastrula, (iii) differentiation and reorganization rhombencephalon. Later, in development, the CNS will go of the progenitor cells into tissues and organs, (iv) full growth through a stage termed ‘five vesicles’, namely telencephalon, of the organs and (v) birth. diencephalon, mesencephalon, metencephalon and myelen- In the course of development, cell differentiation begins with cephalon. From the telencephalon originates the cerebral the emergence of the cells in the three primordial layers of the cortex, basal ganglia, hippocampal formation, amygdala and gastrula: the ectoderm (outer layer), the mesoderm (middle olfactory bulb, and from the diencephalon the thalamus and layer) and the endoderm (inner layer). Roughly speaking, the surrounding nuclei, hypothalamus, retina and optic nerve. gastrula ectoderm develops into the skin, the sense organs, and the nervous system. The progenitor cells for all neurons Neural Tube Defects and glial cells of CNS begin as a further differentiation of ectoderm cells into a layer known as the neural plate (see Abnormalities in neural tube formation result in NTDs and Smith and Schoenwolf5 and schematics in Figure 1). The both environmental and genetic factors can lead to NTDs in 1 neural plate folds and differentiates into neural crest cells and in every 1000 births and cause 1 in 20 of every spontaneous a neural tube.
Load more

Recommended publications
  • 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.
    [Show full text]
  • Gastrulation
    Embryology of the spine and spinal cord Andrea Rossi, MD Neuroradiology Unit Istituto Giannina Gaslini Hospital Genoa, Italy [email protected] LEARNING OBJECTIVES: LEARNING OBJECTIVES: 1) To understand the basics of spinal 1) To understand the basics of spinal cord development cord development 2) To understand the general rules of the 2) To understand the general rules of the development of the spine development of the spine 3) To understand the peculiar variations 3) To understand the peculiar variations to the normal spine plan that occur at to the normal spine plan that occur at the CVJ the CVJ Summary of week 1 Week 2-3 GASTRULATION "It is not birth, marriage, or death, but gastrulation, which is truly the most important time in your life." Lewis Wolpert (1986) Gastrulation Conversion of the embryonic disk from a bilaminar to a trilaminar arrangement and establishment of the notochord The three primary germ layers are established The basic body plan is established, including the physical construction of the rudimentary primary body axes As a result of the movements of gastrulation, cells are brought into new positions, allowing them to interact with cells that were initially not near them. This paves the way for inductive interactions, which are the hallmark of neurulation and organogenesis Day 16 H E Day 15 Dorsal view of a 0.4 mm embryo BILAMINAR DISK CRANIAL Epiblast faces the amniotic sac node Hypoblast Primitive pit (primitive endoderm) faces the yolk sac Primitive streak CAUDAL Prospective notochordal cells Dias Dias During
    [Show full text]
  • 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.
    [Show full text]
  • Terminologia Embryologica
    Terminologia Embryologica МЕЖДУНАРОДНЫЕ ТЕРМИНЫ ПО ЭМБРИОЛОГИИ ЧЕЛОВЕКА С ОФИЦИАЛЬНЫМ СПИСКОМ РУССКИХ ЭКВИВАЛЕНТОВ FEDERATIVE INTERNATIONAL PROGRAMME ON ANATOMICAL TERMINOLOGIES (FIPAT) РОССИЙСКАЯ ЭМБРИОЛОГИЧЕСКАЯ НОМЕНКЛАТУРНАЯ КОМИССИЯ Под редакцией акад. РАН Л.Л. Колесникова, проф. Н.Н. Шевлюка, проф. Л.М. Ерофеевой 2014 VI СОДЕРЖАНИЕ 44 Facies Лицо Face 46 Systema digestorium Пищеварительная система Alimentary system 47 Cavitas oris Ротовая полость Oral cavity 51 Pharynx Глотка Pharynx 52 Canalis digestorius; Canalis Пищеварительный канал Alimentary canal oesophagogastrointestinalis 52 Oesophagus Пищевод Oesophagus▲ 53 Gaster Желудок Stomach 54 Duodenum Двенадцатиперстная кишка Duodenum 55 Ansa umbilicalis intestini Пупочная кишечная петля Midgut loop; Umbilical intestinal loop 56 Jejunum et Ileum Тощая и подвздошная кишка Jejunum and Ileum 56 Intestinum crassum Толстая кишка Large intestine 58 Canalis analis Анальный канал Anal canal 58 Urenteron; Pars postcloacalis Постклоакальная часть кишки Postcloacal gut; intestini Tailgut; Endgut 59 Hepar Печень Liver 60 Ductus choledochus; Ductus Жёлчный проток Bile duct biliaris 61 Vesica biliaris et ductus Жёлчный пузырь и пузырный про- Gallbladder and cystic cysticus ток duct 61 Pancreas Поджелудочная железа Pancreas 63 Systema respiratorium Дыхательная система Respiratory system 63 Nasus Нос Nose 64 Pharynx Глотка, зев Pharynx 64 Formatio arboris respiratoriae Формирование дыхательной Formation of системы (бронхиального дерева) respiratory tree 67 Systema urinarium Мочевая система Urinary
    [Show full text]
  • Mechanisms of Programmed Cell Death in the Developing Brain
    _TINS July 2000 [final corr.] 12/6/00 10:39 am Page 291 R EVIEW Mechanisms of programmed cell death in the developing brain Chia-Yi Kuan, Kevin A. Roth, Richard A. Flavell and Pasko Rakic Programmed cell death (apoptosis) is an important mechanism that determines the size and shape of the vertebrate nervous system. Recent gene-targeting studies have indicated that homologs of the cell-death pathway in the nematode Caenorhabditis elegans have analogous functions in apoptosis in the developing mammalian brain.However,epistatic genetic analysis has revealed that the apoptosis of progenitor cells during early embryonic development and apoptosis of postmitotic neurons at later stage of brain development have distinct roles and mechanisms.These results provide new insight on the significance and mechanism of neural cell death in mammalian brain development. Trends Neurosci. (2000) 23, 291–297 ELL DEATH has long been recognized to occur in homologs of ced-3 comprise a family of cysteine- Cmost neuronal populations during normal devel- containing, aspartate-specific proteases called caspases5. opment of the vertebrate nervous system (reviewed in The ced-4 homolog is identified as one of the apoptosis Ref. 1). Traditionally, the investigation of neural death protease-activating factors (APAFs)6. The mammalian in development focused on the role of target-derived homologs of ced-9 belong to a growing family of Bcl2 survival factors such as NGF and related neurotrophins proteins, which share the Bcl2-homology (BH) domain (see Ref. 2 for a review). However, in the past few years, and are either pro- or anti-apoptotic7. The cloning of the genetic analysis of programmed cell death in the egl-1 indicates that it is similar to the BH3-domain- nematode Caenorhabditis elegans has inspired new ap- containing, pro-apoptotic subfamily of Bcl2 proteins4.
    [Show full text]
  • Programmed Cell Death During Xenopus Development
    DEVELOPMENTAL BIOLOGY 203, 36–48 (1998) ARTICLE NO. DB989028 View metadata, citation and similar papers at core.ac.uk brought to you by CORE Programmed Cell Death during Xenopus provided by Elsevier - Publisher Connector Development: A Spatio-temporal Analysis Carmel Hensey and Jean Gautier1 Department of Genetics and Development and Department of Dermatology, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, New York 10032 Programmed cell death (PCD) is an integral part of many developmental processes. In vertebrates little is yet known on the patterns of PCD and its role during the early phases of development, when embryonic tissue layers migrate and pattern formation takes place. We describe the spatio-temporal patterns of cell death during early Xenopus development, from fertilization to the tadpole stage (stage 35/36). Cell death was analyzed by a whole-mount in situ DNA end-labeling technique (the TUNEL protocol), as well as by serial sections of paraffin-embedded TUNEL-stained embryos. The first cell death was detected during gastrulation, and as development progressed followed highly dynamic and reproducible patterns, strongly suggesting it is an important component of development at these stages. The detection of PCD during neural induction, neural plate patterning, and later during the development of the nervous system highlights the role of PCD throughout neurogenesis. Additionally, high levels of cell death were detected in the developing tail and sensory organs. This is the first detailed description of PCD throughout early development of a vertebrate, and provides the basis for further studies on its role in the patterning and morphogenesis of the embryo.
    [Show full text]
  • Embryology and Teratology in the Curricula of Healthcare Courses
    ANATOMICAL EDUCATION Eur. J. Anat. 21 (1): 77-91 (2017) Embryology and Teratology in the Curricula of Healthcare Courses Bernard J. Moxham 1, Hana Brichova 2, Elpida Emmanouil-Nikoloussi 3, Andy R.M. Chirculescu 4 1Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, Wales, United Kingdom and Department of Anatomy, St. George’s University, St George, Grenada, 2First Faculty of Medicine, Institute of Histology and Embryology, Charles University Prague, Albertov 4, 128 01 Prague 2, Czech Republic and Second Medical Facul- ty, Institute of Histology and Embryology, Charles University Prague, V Úvalu 84, 150 00 Prague 5 , Czech Republic, 3The School of Medicine, European University Cyprus, 6 Diogenous str, 2404 Engomi, P.O.Box 22006, 1516 Nicosia, Cyprus , 4Department of Morphological Sciences, Division of Anatomy, Faculty of Medicine, C. Davila University, Bucharest, Romania SUMMARY Key words: Anatomy – Embryology – Education – Syllabus – Medical – Dental – Healthcare Significant changes are occurring worldwide in courses for healthcare studies, including medicine INTRODUCTION and dentistry. Critical evaluation of the place, tim- ing, and content of components that can be collec- Embryology is a sub-discipline of developmental tively grouped as the anatomical sciences has biology that relates to life before birth. Teratology however yet to be adequately undertaken. Surveys (τέρατος (teratos) meaning ‘monster’ or ‘marvel’) of teaching hours for embryology in US and UK relates to abnormal development and congenital medical courses clearly demonstrate that a dra- abnormalities (i.e. morphofunctional impairments). matic decline in the importance of the subject is in Embryological studies are concerned essentially progress, in terms of both a decrease in the num- with the laws and mechanisms associated with ber of hours allocated within the medical course normal development (ontogenesis) from the stage and in relation to changes in pedagogic methodol- of the ovum until parturition and the end of intra- ogies.
    [Show full text]
  • Junctional Neurulation: a Unique Developmental Program Shaping a Discrete Region of the Spinal Cord Highly Susceptible to Neural Tube Defects
    13208 • The Journal of Neuroscience, September 24, 2014 • 34(39):13208–13221 Development/Plasticity/Repair Junctional Neurulation: A Unique Developmental Program Shaping a Discrete Region of the Spinal Cord Highly Susceptible to Neural Tube Defects Alwyn Dady,1,2 X Emmanuelle Havis,1,2 Virginie Escriou,3 Martin Catala,1,2,4 and Jean-Loup Duband1,2 1Universite´ Pierre et Marie Curie-Paris 6, Laboratoire de Biologie du De´veloppement, 75005 Paris, France, 2Centre National de la Recherche Scientifique, Laboratoire de Biologie du De´veloppement, 75005 Paris, France, 3Unite´ de Technologies Chimiques et Biologiques pour la Sante´, Centre National de la Recherche Scientifique Unite´ Mixte de Recherche 8258, Institut National de la Sante´ et de la Recherche Me´dicale U1022, Universite´ Paris Descartes, Faculte´ de Pharmacie, 75006 Paris, France, and 4Assistance Publique-Hopitaux de Paris, Federation of Neurology, Groupe Hospitalier Pitie´-Salpeˆtrie`re, 75013 Paris, France In higher vertebrates, the primordium of the nervous system, the neural tube, is shaped along the rostrocaudal axis through two consecutive, radically different processes referred to as primary and secondary neurulation. Failures in neurulation lead to severe anomalies of the nervous system, called neural tube defects (NTDs), which are among the most common congenital malformations in humans. Mechanisms causing NTDs in humans remain ill-defined. Of particular interest, the thoracolumbar region, which encompasses many NTD cases in the spine, corresponds to the junction between primary and secondary neurulations. Elucidating which developmen- tal processes operate during neurulation in this region is therefore pivotal to unraveling the etiology of NTDs. Here, using the chick embryo as a model, we show that, at the junction, the neural tube is elaborated by a unique developmental program involving concerted movements of elevation and folding combined with local cell ingression and accretion.
    [Show full text]
  • Mechanics-Guided Embryonic Patterning of Neuroectoderm Tissue from Human Pluripotent Stem Cells
    ARTICLES https://doi.org/10.1038/s41563-018-0082-9 Mechanics-guided embryonic patterning of neuroectoderm tissue from human pluripotent stem cells Xufeng Xue1,9, Yubing Sun1,2,9*, Agnes M. Resto-Irizarry1, Ye Yuan3, Koh Meng Aw Yong1, Yi Zheng1, Shinuo Weng 1, Yue Shao 1, Yimin Chai4, Lorenz Studer5,6 and Jianping Fu 1,7,8* Classic embryological studies have successfully applied genetics and cell biology principles to understand embryonic develop- ment. However, it remains unresolved how mechanics, as an integral driver of development, is involved in controlling tissue-scale cell fate patterning. Here we report a micropatterned human pluripotent stem (hPS)-cell-based neuroectoderm developmental model, in which pre-patterned geometrical confinement induces emergent patterning of neuroepithelial and neural plate border cells, mimicking neuroectoderm regionalization during early neurulation in vivo. In this hPS-cell-based neuroectoderm pattern- ing model, two tissue-scale morphogenetic signals—cell shape and cytoskeletal contractile force—instruct neuroepithelial/ neural plate border patterning via BMP-SMAD signalling. We further show that ectopic mechanical activation and exogenous BMP signalling modulation are sufficient to perturb neuroepithelial/neural plate border patterning. This study provides a use- ful microengineered, hPS-cell-based model with which to understand the biomechanical principles that guide neuroectoderm patterning and hence to study neural development and disease. ne of the enduring mysteries of biology is tissue morpho- on glass coverslips (Fig. 1a and Supplementary Fig. 1). H1 human genesis and patterning, where embryonic cells act in a embryonic stem (hES) cells were plated as single cells at 20,000 coordinated fashion to shape the body plan of multicellu- cells cm−2 on adhesive islands to establish micropatterned colonies O 1–5 lar animals .
    [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]
  • The Ectoderm: Neurulation, Neural Tube, Neural Crest
    Events that remove cells Progressive restriction from the epidermal of developmental lineage potential The ectoderm: neurulation, neural tube, neural crest Taube P. Rothman [email protected] Neural Shaping the neural plate induction 18 days PRIMARY NEURULATION Neural induction, Wnt Wnt formation of the neural plate Dorsal and Wnt Wnt ventral Formation of of the neural signaling in the groove and neural folds spinal cord Closure of neural Neural crest folds, formation of neural tube and neural crest Initially, the neural tube is composed of a single layer of neuroepithelial cells 1 Dorsal view: Neurulating embryos Dorsal view: Neurulating embryos REGIONS OF NEURAL TUBE CLOSURE Days 21-22 Day 23 cranioschisis meningomyecele REGIONALIZATION OF THE CNS PRIMARY AND SECONDARY VESICLES AND FLEXURES Cephalic Rhombomere flexure Cervical flexure NEUROGENESIS IN THE NEUROEPITHELIUM How are billions of CNS cells (neurons and glia) generated? lumen Cerebral cortex lumen Post mitotic daughter cell Lumen Nuclei (but not cells) migrate during the cell The plane of division of progenitor cells in the cycle ventricular zone influences their fate The neuroepithelium is a single layer of rapidly dividing stem cells 2 At least half the neurons that are generated undergo apoptosis and die. Neuronal survival depends upon recognition of target related trophic signals. Ectomesenchyme The neural crest Neural crest cells are guided through permissive Wnt BMP environments to RhoB reach their targets slug Ephrin proteins inhibit neural crest migration THE REGION OF THE NEURAXIS FROM WHICH A CREST CELL MIGRATES DETERMINES THE TARGET REACHED BY ITS DERIVATIVES cranial circumpharyngeal neural crest truncal cardiac vagal truncal sacral 3 Genetic potential, developmental restriction and differentiation •Some neural crest cells appear to be pluripotent.
    [Show full text]
  • 26 April 2010 TE Prepublication Page 1 Nomina Generalia General Terms
    26 April 2010 TE PrePublication Page 1 Nomina generalia General terms E1.0.0.0.0.0.1 Modus reproductionis Reproductive mode E1.0.0.0.0.0.2 Reproductio sexualis Sexual reproduction E1.0.0.0.0.0.3 Viviparitas Viviparity E1.0.0.0.0.0.4 Heterogamia Heterogamy E1.0.0.0.0.0.5 Endogamia Endogamy E1.0.0.0.0.0.6 Sequentia reproductionis Reproductive sequence E1.0.0.0.0.0.7 Ovulatio Ovulation E1.0.0.0.0.0.8 Erectio Erection E1.0.0.0.0.0.9 Coitus Coitus; Sexual intercourse E1.0.0.0.0.0.10 Ejaculatio1 Ejaculation E1.0.0.0.0.0.11 Emissio Emission E1.0.0.0.0.0.12 Ejaculatio vera Ejaculation proper E1.0.0.0.0.0.13 Semen Semen; Ejaculate E1.0.0.0.0.0.14 Inseminatio Insemination E1.0.0.0.0.0.15 Fertilisatio Fertilization E1.0.0.0.0.0.16 Fecundatio Fecundation; Impregnation E1.0.0.0.0.0.17 Superfecundatio Superfecundation E1.0.0.0.0.0.18 Superimpregnatio Superimpregnation E1.0.0.0.0.0.19 Superfetatio Superfetation E1.0.0.0.0.0.20 Ontogenesis Ontogeny E1.0.0.0.0.0.21 Ontogenesis praenatalis Prenatal ontogeny E1.0.0.0.0.0.22 Tempus praenatale; Tempus gestationis Prenatal period; Gestation period E1.0.0.0.0.0.23 Vita praenatalis Prenatal life E1.0.0.0.0.0.24 Vita intrauterina Intra-uterine life E1.0.0.0.0.0.25 Embryogenesis2 Embryogenesis; Embryogeny E1.0.0.0.0.0.26 Fetogenesis3 Fetogenesis E1.0.0.0.0.0.27 Tempus natale Birth period E1.0.0.0.0.0.28 Ontogenesis postnatalis Postnatal ontogeny E1.0.0.0.0.0.29 Vita postnatalis Postnatal life E1.0.1.0.0.0.1 Mensurae embryonicae et fetales4 Embryonic and fetal measurements E1.0.1.0.0.0.2 Aetas a fecundatione5 Fertilization
    [Show full text]