Development of Cns, Ans and Sense Organs
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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. -
Sox9 Is Required for Invagination of the Otic Placode in Mice ⁎ Francisco Barrionuevo A, , Angela Naumann B, Stefan Bagheri-Fam A,1, Volker Speth C, Makoto M
Available online at www.sciencedirect.com Developmental Biology 317 (2008) 213–224 www.elsevier.com/developmentalbiology Sox9 is required for invagination of the otic placode in mice ⁎ Francisco Barrionuevo a, , Angela Naumann b, Stefan Bagheri-Fam a,1, Volker Speth c, Makoto M. Taketo d, Gerd Scherer a, Annette Neubüser b a Institute of Human Genetics and Anthropology, University of Freiburg, Breisacherstr. 33, D-79106 Freiburg, Germany b Developmental Biology, Institute of Biology 1, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany c Cell Biology, Institute of Biology II, University of Freiburg, Schänzlestrasse 1, D-79104 Freiburg, Germany d Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoé-cho, Sakyo-ku, Kyoto 606-8501, Japan Received for publication 20 December 2007; revised 7 February 2008; accepted 8 February 2008 Available online 21 February 2008 Abstract The HMG-domain-containing transcription factor Sox9 is an important regulator of chondrogenesis, testis formation and development of several other organs. Sox9 is expressed in the otic placodes, the primordia of the inner ear, and studies in Xenopus have provided evidence that Sox9 is required for otic specification. Here we report novel and different functions of Sox9 during mouse inner ear development. We show that in mice with a Foxg1Cre-mediated conditional inactivation of Sox9 in the otic ectoderm, otic placodes form and express markers of otic specification. However, mutant placodes do not attach to the neural tube, fail to invaginate, and subsequently degenerate by apoptosis, resulting in a complete loss of otic structures. Transmission-electron microscopic analysis suggests that cell–cell contacts in the Sox9 mutant placodes are abnormal, although E-cadherin, N-cadherin, and beta-catenin protein expression are unchanged. -
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. -
And Krox-20 and on Morphological Segmentation in the Hindbrain of Mouse Embryos
The EMBO Journal vol.10 no.10 pp.2985-2995, 1991 Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos G.M.Morriss-Kay, P.Murphy1,2, R.E.Hill1 and in embryos are unknown, but in human embryonal D.R.Davidson' carcinoma cells they include the nine genes of the Hox-2 cluster (Simeone et al., 1990). Department of Human Anatomy, South Parks Road, Oxford OXI 3QX The hindbrain and the neural crest cells derived from it and 'MRC Human Genetics Unit, Western General Hospital, Crewe are of particular interest in relation to the developmental Road, Edinburgh EH4 2XU, UK functions of RA because they are abnormal in rodent 2Present address: Istituto di Istologia ed Embriologia Generale, embryos exposed to a retinoid excess during or shortly before Universita di Roma 'la Sapienza', Via A.Scarpa 14, 00161 Roma, early neurulation stages of development (Morriss, 1972; Italy Morriss and Thorogood, 1978; Webster et al., 1986). Communicated by P.Chambon Human infants exposed to a retinoid excess in utero at early developmental stages likewise show abnormalities of the Mouse embryos were exposed to maternally administered brain and of structures to which cranial neural crest cells RA on day 8.0 or day 73/4 of development, i.e. at or just contribute (Lammer et al., 1985). Retinoid-induced before the differentiation of the cranial neural plate, and abnormalities of hindbrain morphology in rodent embryos before the start of segmentation. On day 9.0, the RA- include shortening of the preotic region in relation to other treated embryos had a shorter preotic hindbrain than the head structures, so that the otocyst lies level with the first controls and clear rhombomeric segmentation was pharyngeal arch instead of the second (Morriss, 1972; absent. -
20. Placodes and Sensory Development
PLACODES AND 20. SENSORY DEVELOPMENT Letty Moss-Salentijn DDS, PhD Dr. Edwin S. Robinson Professor of Dentistry (in Anatomy and Cell Biology) E-mail: [email protected] READING ASSIGNMENT: Larsen 3rd Edition Chapter 12, Part 2. pp.379-389; Part 3. pp.390- 396; Chapter 13, pp.430-432 SUMMARY A series of ectodermal thickenings or placodes develop in the cephalic region at the periphery of the neural plate. Placodes are central to the development of the cranial sensory systems in vertebrates and are among the innovations that appeared in the early evolution of vertebrates. There are placodes for the three organs of special sense: olfactory, optic (lens) and otic placodes, and (epibranchial) placodes that give rise to the distal cells of the sensory ganglia of cranial nerves V, VII, IX and X. Placodes (with the possible exception of the olfactory placodes) form under the influence of surrounding cranial tissues. They do not appear to require the presence of neural crest. The mesoderm in the prechordal plate plays a significant role in the initial development of the placodes for the organs of special sense, while the pharyngeal pouch endoderm plays that role in the development of the epibranchial placodes. The development of the organs of special sense is described briefly. LEARNING OBJECTIVES You should be able to: a. Give a definition of placodes and describe their evolutionary significance. b. Name the different types of placodes, their locations in the developing embryo and their developmental fates. c. Discuss the early development of the placodes and some of the possible factors that feature in their development. -
Cephalic Neurulation in the Mouse Embryo Analyzed by SEM and Morphometry
THE ANATOMICAL RECORD 203:375-396 (1982) Cephalic Neurulation in the Mouse Embryo Analyzed by SEM and Morphometry ANTONE G. JACOBSON AND PATRICK P.L. TAM Department of Zoology. Uniuersity of Texas, Austin, TX 78712 (A.G.J.) and Department of Anatomy, (‘hinese University of Hong Kong, Shatin, N.T., Hong Kong IP.PL.T) ABSTRACT A detailed account of mouse neurulation is given based mostly on SEM analysis over 20 hr of development. Many observations and measure- ments were made on staged living embryos and on embryos prepared for scanning and light microscopy to help deduce what mechanisms may contribute to neural tube formation. Each lateral half of the early cephalic neural plate makes a convex bulge, opposite to the way it must fold to form a tube. Underlying mesenchyme and matrix are reported to have a role in forming these bulges. Processes that form the tube must overcome this opposed folding and the forces that produce it. Crani- al flexure begins long before tube formation. The flexure commences at the rostra1 tip of the cephalic neural plate, then the apex of the flexure migrates caudally to the mesencephalic region. Early appearance of this flexure imposes a mechanical impediment to tube closure in forebrain and midbrain regions. Tube closure begins in the cervical region exactly where the neural plate is reflected dorsally by a bend in the embryo. This bend may mechanically assist closure in this region. Cells of the mouse neural plate are reported to contain organized microfilaments and mi- crotubules, and the plate cells appear to change shape (reduce apical area and in- crease cell height) in the same manner as that suggested in embryos of some other species to contribute to neural tube formation. -
CENTRÁLNÍ a PERIFERNÍ NERVOVÝ SYSTÉM Mikroskopická Stavba A
Embryology /organogenesis/ Development and teratology of nervous system. NOTOCHORD Neuroectoderm DEVELOPMENT Neural plate NOTOCHORD - induces neural plate development 2 Neural plate – thickened area of embryonic ectoderm neuroectoderm pseudostratif. columnar ep. Pharyngeal membrane Primitive streak and node Notochord Cloacal membrane 3 NEURULATION – invagination of neural plate (day 16 - 24) - neural folds - neural groove - neural tube - neural crest 4 notochord Day 20 Neural folds 5 Day 22, 23 Neuroporus anterior closes on D 25 closes on D 27 Neuroporus posterior 6 NEURAL CREST 7 Odontoblasts Leptomeningeal cells 8 EKTOMESENCHYME 9 Histogenesis of neural tube The wall of neural tube: (simple → pseudostratified neural epithelium) Cell proliferation 3 zones: Ependymal Intermediate Marginal zone Ependyma Gray matter White matter10 (in medulla spinalis) HISTOGENESIS of NEURAL TUBE Marginal zone (white matter) Intermediate zone (gray matter) (mantle zone) Ependymal zone (germinal) 11 Histogenesis of neural tissue In spinal cord white matter gray matter ependyme Three zones line neural tube (the spinal cord and brain stem). Marginal zone (white matter) – without neurons, but with axons of neurons and glial cells Mantle zone (gray matter) – neuroblasts + spongioblasts give rise to bodies of neurons and glial cells Ependymal zone (germinal) – lining of central canal 12 In brain and cerebellum gray matter white matter ependyme In brain and cerbellum: mantle zone cells migrate through marginal layer and the gray matter coveres white matter. Some neurons stay in white matter nuclei. 13 Spinal cord development Dorsal horns future white matter sensory zone future gray matter motor zone Ventral horns 14 SPINAL CORD: 1. Ependymal layer (germinal) 2. Mantle layer (gray matter) 3. -
Otic Capsule Or Bony Labyrinth
DEVELOPMENT OF EAR BY DR NOMAN ULLAH WAZIR DEVELOPMENT OF EAR The ears are composed of three anatomic parts: External ear: • Consisting of the auricle , external acoustic meatus, and the external layer of the tympanic membrane. Middle ear: • The internal layer of the tympanic membrane, and three small auditory ossicles, which are connected to the oval windowsof the internal ear. • Internal ear: Consisting of the vestibulocochlear organ, which is concerned with hearing and balance. • The external and middle parts of the ears are concerned with the transference of sound waves to the internal ears, which convert the waves into nerve impulses and registers changes in equilibrium. DEVELOPMENT OF INTERNALEAR The internal ears are the first to develop. • Otic placode: Early in the 4th week, a thickening of surface ectoderm takes place on each side of the myelencephalon,the caudal part of thehindbrain. • Inductive signals from the paraxial mesoderm and notochord stimulate the surface ectoderm to form theplacodes. • Each otic placode soon invaginates and sinks deep to the surface ectoderm into the underlying mesenchyme. • In so doing, it forms an otic pit. • The edges of the pit come together and fuse to forman otic vesicle the primordium of the membranous labyrinth. • The otic vesicle soon loses its connection with the surface ectoderm. • A diverticulum (endolymohatic appendage) grows from the vesicle and elongates to form the endolymphatic duct and sac. the rest of the oticvesicle differentiates into an expanded pars superior (Ventral saccularparts, which give rise to the sacculeand cochlearducts) and an initially tapered pars inferior (Dorsal utricular parts, from which thesmall endolymphaticducts, utricles and semicircular ductsarise). -
Olfactory Epithelium: Development of the Nose Olfactory Epithelium: Development of the Nose
DEVELOPMENT OF THE HEAD AND NECK PlacodesPlacodes andand thethe developmentdevelopment ofof organsorgans ofof specialspecial sensesense LL.. MMoossss--SaSalelentijnntijn Innovations in the early evolution of vertebrates ! DDeevveellooppmmeenntt ooff oorrggaannss ooff ssppeecciiaall sseennssee ((ppllaaccooddeess)) ! DDeevveellooppmmeenntt ooff aa llaarrggee nneeuurraall cciirrccuuiittrryy ((tthhee bbrraaiinn)) ttoo iinntteeggrraattee iinnppuutt aanndd rreessppoonnsseess ! DDeevveellooppmmeenntt ooff aann eeffffeeccttiivvee ffeeeeddiinngg aappppaarraattuuss (jaws)(jaws) ! DDeevveellooppmmeenntt ooff aann iimmpprroovveedd rreessppiirraattoorryy aappppaarraattuuss ((ggiillllss)) PLACODES Localized thickened areas of specialized ectoderm, lateral to the neural crest, at the border between neural plate and the future epidermis Brugmann SA, Moody SA (2005) Brugmann SA, Moody SA (2005) NEURAL PLATE NEURAL GROOVE Example: otic placode. Different kinds of placodes ! CCoonnttrriibbuuttiinngg ttoo oorrggaannss ooff ssppeecciiaall sseennssee:: "OlfactoryOlfactory "LensLens (only(only placodeplacode thatthat doesdoes notnot havehave neuralneural fate)fate) "OticOtic ! ContributingContributing toto distaldistal gangliaganglia ofof branchiomericbranchiomeric nneerrvveess:: "TrigeminalTrigeminal (Ophthalmic,V1)(Ophthalmic,V1) "EpibranchialEpibranchial (4)(4) ! Hypobranchial (2) (contribute to hypobranchial ganglia - frog only; not in chick, mouse, zebrafish) Distribution of placodes at 3 developmental stages A. Initial induction of placodes in pre-placodal -
Flexion and Neural Tube Formation
Flexion and Neural Tube Formation RECOMMENDED READING: Larsen: Human Embryology 3rd edition 1. Review figures 2.4-2.6 and such text as necessary (pp 41-43 for source of definitive yolk sac and extra-embryonic coelom (cavity). 2. Pp 131-143. Text covers the formation of the intra-embryonic coelom and its division into peritoneal, pleural and pericardial cavities plus closure of the diaphragm. 3. Pp 57, Figure 3-4; pp 85-93. Text covers the transformation of the neural plate into the neural tube, the initial phases of differentiation of this tube and the origin of the neural crest. The multiple fates of neural crest derivatives will be given in other lectures. LEARNING OBJECTIVES: 1.Review information on the formation of the extra-embryonic coelom from prior lecture. Embryonic flexion and folding 2. Understand how the lateral plate mesoderm divides into somatopleure and splanchnopleure, which flex (fold) in the lateral plane and fuse ventrally. This results in the enclosure of some of the extra-embryonic coelom into the embryo. 3. Note that head/tail flexion is "driven" in part by rapid growth of the CNS and relative stiffness of notochord. 4. Understand the "accomplishments" of flexion and folding: a. Segregation of embryonic from extra-embryonic tissues except at umbilical cord. b. Enclosure the intra-embryonic coelom. c. Narrowing of the gut tube. d. Postioning of the buccopharyngeal membrane (future mouth) and cloacal membrane (future opening of urinary and gastrointestinal tracts) to a ventral position. e. "Movement" of the septum transversum and cardiogenic tissues ventrally. Formation of and closure of the neural tube, division into primary brain vesicles and origin of neural crest. -
Flexion [Recovered]
Embryonic Flexion and Folding Bilaminar embryo End of gastrulation Remember placement of heart primordium The lateral plate mesoderm splits. Each leaf will fold toward midline. Narrowing yolk sac and gut & enclosing coelom. Note how amnion follows embryonic folding. Narrowing of gut tube and yolk sac. Folding complete: midgut remains open to vitelline duct Foregut is initially suspended by dorsal and ventral mesentery. Ventral mesentery reabsorbed. Dorsal remains. Organ in intraperitoneal. Intraembryonic coelom continues anterior of the heart primordium. What is different about the embryo after flexion? Embryonic sources of adult diaphragm The ectoderm: neurulation, neural tube, neural crest Neural tissue is said to be induced by mesodermal tissue Signals divert midline ectoderm from an ectodermal fate. Shaping the neural plate PRIMARY NEURULATION Neural induction, formation of the neural plate Formation of of the neural groove and neural folds 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 Dorsal view Ventral view Days 21-22 Day 23 REGIONS OF NEURAL TUBE CLOSURE How are billions of CNS cells (neurons and glia) generated? The neuroepithelium is a layer of rapidly dividing stem cells. What are the mechanisms for dispersal of cells from the ventricular layer? NEUROGENESIS IN THE CEREBRAL CORTEX Cerebral cortex 1. Developing post-mitotic neuroblasts use special glial cells and their processes as migration paths. 2. Neurons born at early stages migrate to the deepest layers of the cortical plate. 3. Neurons born at later stages form the more superficial layers of the cortex. -
For Proteoglycans in Neurulation
J. Anat. (1982), 134, 3, pp. 491-506 491 With 16figures Printed in Great Britain Culture of rat embryos with p-D-xyloside: evidence of a role for proteoglycans in neurulation GILLIAN M. MORRISS-KAY AND BETH CRUTCH Department ofHuman Anatomy, University of Oxford (Accepted 1 May 1981) INTRODUCTION The synthesis of sulphated glycosaminoglycans by early post-implantation rat embryos occurs at very low levels until the onset of neurulation, at which time there is an increase in the level ofsynthesis (as indicated by [3H]glucosamine incorporation) of chondroitin/chondroitin sulphate and heparan sulphate (Solursh & Morriss, 1977). In embryos undergoing neurulation, histochemical staining techniques have indicated that these sulphated glycosaminoglycans are localised in the ectodermal basement membrane and in the extracellular matrix and cell surface-associated material of the mesenchyme. The staining intensity is higher in the neural fold region than elsewhere in the embryo. They are probably present in the form of proteoglycan in association with hyaluronate (Morriss & Solursh, 1978a). In order to investigate further these stage and position-related histochemical differences, we have cultured rat embryos in vitro during neurulation and early somitogenesis in the presence of the xylose-derivative, /8-D-xyloside. This substance has been shown to bring about a reduction in the level of synthesis of protein-bound chondroitin sulphate and an increase in free chondroitin sulphate chains in both chondrogenic and non-chondrogenic systems (Schwartz, Ho & Dorfman, 1976; Galligani, Hopwood, Schwartz & Dorfman, 1975). Its activity is due to interference with the sequence of normal chondroitin sulphate-proteoglycan synthesis, as fol- lows. Prior to chondroitin sulphate chain synthesis, three sugar molecules, xylose and two galactose molecules, are added sequentially to certain serines of the core protein (for review, see Roden & Schwartz, 1975).