DOCSLIB.ORG

Spatially and Temporally Restricted Expression of Pax2 During Murine Neurogenesis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Spatially and Temporally Restricted Expression of Pax2 During Murine Neurogenesis Development 109, 797-809 (1990) 797 Printed in Great Britain ©The Company of Biologists Limited 1990 Spatially and temporally restricted expression of Pax2 during murine neurogenesis HOWARD O. NORNES*, GREGORY R. DRESSLERf, ELZBIETAW. KNAPIK, URBAN DEUTSCH and PETER GRUSS* Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, 3400 GOttingen, FRG *On leave from the Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, Colorado 80523, USA t Present address: Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892, USA X Corresponding author Summary The expression of the murine paired-box-containing optic cup and stalk and later to the optic disc and nerve. gene, Pax2, is examined in the developing central In the ear, expression is restricted to regions of the otic nervous system by in situ hybridization. Pax2 ex- vesicle that form neuronal components. The transient pression is detected along the boundaries of primary and restricted nature of Pax2 expression suggests that divisions of the neural tube. Initially, Pax2 is expressed this murine segmentation gene homologue may also in the ventricular zone in two compartments of cells on establish compartmental boundaries and contribute to either side of the sulcus limitans and along the entire the specification of neuronal identity, as do certain rhombencephalon and spinal cord. At later times, Pax2 Drosophila segmentation genes. is restricted to progeny cells that have migrated to specific regions of the intermediate zone. In the eye, Key words: neurogenesis, paired box, Pax, optic vesicle, Pax2 expression is restricted to the ventral half of the otic vesicle, mouse embryology. Introduction protein is expressed in a segmented pattern of seven stripes at the blastoderm stage and fifteen clusters of The mammalian central nervous system is a highly germ band nuclei in the developing nervous system at evolved network of interconnected cells designed to the early gastrulation stage (Carroll and Scott, 1985). In sense, store and process information. Implicit in its fact, a specific neurogenic regulatory element controls design is a precise architecture, the foundation of which ftz expression at this stage (Hiromi et al. 1985). More is laid down during embryogenesis. How the develop- recent experiments point to a defined transformation of ment of the mammalian nervous system is regulated a neuronal phentoype mftz mutants (Doe et al. 1988a). and what genes encode determining factors for cell and Similar observations were also made in temperature- positional specification remain unknown. However, sensitive mutants of the Drosophila pair-rule gene even- recent experiments with Drosophila embryos demon- skipped (eve) (Doe et al. 1988ft). These neurogenic strate that certain genes controlling the segmentation of functions are not exclusive to segmentation genes of the the embryo also affect neurogenesis and, in particular, pair-rule class, as the segment polarity mutants goose- neuronal identities (Doe et al. 1988a,b; Patel et al. berry, patched, cell and wingless also exhibit altered 1989). neuronal identities (Patel et al. 1989). Segmentation in Drosophila is controlled by the Many segmentation and homeotic genes of Dros- sequential activation of the gap, pair-rule and segment ophila share highly conserved protein domains that polarity genes (Niisslein-Volhard and Wieschaus, 1980; have enabled investigators to isolate vertebrate genes for review see Ingham, 1988; Akam, 1987; Scott and with similar domains (for reviews see: Dressier and Carroll, 1987). First expressed at the cellular blasto- Gruss, 1988; Wright et al. 1989). The Pax2 gene was derm stage, the Drosophila pair-rule genes are also identified (Dressier et al. 1990) through its homology to expressed during neurogenesis. Thus, a gene that func- the paired box found amongst the Drosophila segmen- tions in the establishment of a segmented body plan is tation genes paired, gooseberry-proximal, gooseberry- also required for nervous system development from the distal, Pox meso and Pox neuro (Bopp et al. 1986; 1989). neuroectoderm. For example, the fushi tarazu (ftz) The Pax2 gene is expressed in the developing excretory 798 H. O. Nornes and others system (Dressier et al. 1990), a transiently segmented plane of the spinal cord during two phases: the periods structure of mesodermal origin. In addition, this report of (1) neurogenesis and (2) post neurogenesis. Based on describes the spatial and temporal expression pattern of [3H]thymidine analysis, neurons in the mouse spinal Pax2 during neuronal differentiation in the central cord originate on days 9 to 13 (Nornes and Carry, 1978; nervous system, in defined regions of the otic vesicle, Sims and Vaugh, 1979; McConnell, 1981). During this and during morphogenesis and axonal elongation of the period, the pseudostratified cells in the neuroepi- optic cup and stalk. Thus Pax2 shares not only the thelium (ventricular zone) are mitotically active. In a conserved paired domain with some Drosophila seg- precise ventral-to-dorsal order, the cells stop cycling mentation genes, but also a similar biphasic expression mitotically, and migrate from the margin of the lumen pattern during morphogenesis of segmented structures radially to settle in the surrounding mantle layer (inter- and neurogenesis. mediate zone). For details on this pattern of cell kinetics in the developing mouse spinal cord refer to Nornes and Carry (1978). Materials and methods Pax2 expression during neurogenesis The procedure for in situ hybridization is as described in detail On day 10 of gestation, Pax2 hybridization is detected in the preceding report (Dressier et al. 1990). Pregnant in two regions of the ventricular zone, one on either females were sacrificed at 8-18 days post coitum (p.c); the side of the ventrodorsal midline, the sulcus limitans day of the vaginal plug was designated as day 0. (Fig. 2A,B). It is restricted to the basal region (distal to Both antisense and sense mRNA were synthesized from a lumen) of the neuroepithelium and is more extensive in unique Pax2 cDNA fragment downstream from the paired box sequence to prevent potential cross hybridization with the basal plate than in its counterpart in the alar plate. other paired box containing genes (Dressier et al. 1990). In In the basal plate, the silver grains extend further along addition, a mouse Hox 3.1 probe was used as a positive the ventrodorsal axis as well as further medially towards control (Breier et al. 1988). the apical (luminal) region of the neuroepithelial cells. Pax2 transcripts were never detected in the cells in the ventral 1/4 of the ventricular zone as well as in their Results progeny which settles in the most ventral and lateral intermediate zone and form motor neurons (Nornes The expression of Pax2 was analyzed in various stages and Carry, 1978). of mouse embryogenesis by in situ hybridization. Pax2 On day 11.0 of gestation, Pax2 transcripts in the transcripts were detected in embryo tissue sections from ventricular zone are still restricted to these same two days 9-18 post coitum and were restricted to four compartments bordering the sulcus limitans different epithelial structures: embryonic kidney, (Fig. 2C,D, arrow). The hybridization is more intense neural tube, optic and otic vesicles. Pax2 transcripts and extensive than on the previous day, particularly in were not detected in adult structures examined, includ- the alar plate component, as it extends further dorsally. ing the spinal cord, diencephalon and optic tract (data By this stage, more cells have migrated from the not shown). The structure of the Pax2 cDNA and its ventricular zone and the intermediate zone is now expression in the developing kidney is described in the present in both the basal and alar plates. A few clusters accompanying paper (Dressier et al. 1990), whereas this of silver grains are present in this zone immediately paper describes Pax2 expression in the developing radial to the position of transcripts in the ventricular nervous system. zone (Fig. 2D arrowheads). At day 8 p.c, Pax2 RNA could not be detected in any On day 11.5 of gestation, Pax2 transcripts in the ectodermal or mesodermal structures (data not shown). ventricular zone are no longer restricted to two com- Pax2 expression on day 9 of gestation is detected in partments on either side of the sulcus limitans but are both the optic and otic vesicles as will be described in expressed continuously along the entire dorsal two- detail in the following sections. The earliest detectable thirds of this layer (Fig. 2E,F). In the intermediate expression of Pax2 within the neural tube is during the zone, Pax2 is expressed in the progeny cells that early stages of neuronal differentiation on day 10 of expressed Pax2 on the previous day and is restricted to gestation. two regions extending radially on both sides of the sulcus limitans. In the basal plate, the signal is seen over Neural tube cells that have settled medial and dorsal to the nonex- Overall pattern pressing and earlier formed putative motor neuroblasts Beginning at day 10, Pax2 transcripts are expressed (Fig. 2F arrowheads). In the alar plate, transcripts are along the boundaries of two primary divisions in the present over the entire intermediate zone with the neural tube. The rostral limit of Pax2 expression was at highest density of silver grains along its most lateral the mesencephalon-rhombencephalon border, the isth- border. mus (Fig. 1A,B arrow) and expression extended On day 12 of gestation, the ventricular zone has through the rhombencephalon and spinal cord, on both nearly completely regressed in the basal plate and sides of the sulcus limitans (Fig. 1C,D). This pattern of become thinner in the alar plate (Fig. 2G). In what expression persists in these cells and their progeny from remains of the ventricular zone, Pax2 transcripts are days 10 to 18 and is described in detail in the transverse still expressed in the dorsal two-thirds; however, the Pax2 during neurogenesis 799 Fig.
Load more

Recommended publications
  • The Morphogenesis of the Zebrafish Eye, Including a Fate Map of The
    DEVELOPMENTAL DYNAMICS 218:175–188 (2000) The Morphogenesis of the Zebrafish Eye, Including a Fate Map of the Optic Vesicle ZHENG LI, NANCY M. JOSEPH, AND STEPHEN S. EASTER, JR.* Biology Department, University of Michigan, Ann Arbor, Michigan ABSTRACT We have examined the morpho- The morphogenesis of the zebrafish eye, described by genesis of the zebrafish eye, from the flat optic Schmitt and Dowling (1994), is similar, but different in vesicle at 16 hours post fertilization (hpf) to the some respects. Their scanning electron micrographs of functional hemispheric eye at 72 hpf. We have skinned embryos provided excellent views of the eye, produced three-dimensional reconstructions and revealed that the vesicle bypassed the spherical from semithin sections, measured volumes and stage; when discerned at about 14 hours post fertiliza- areas, and produced a fate map by labeling clus- tion (hpf), the vesicle was a flattened wing-like struc- ters of cells at 14–15 hpf and finding them in the ture. The “wing” was initially attached to the neural 24 hpf eye cup. Both volume and area increased tube over most of its length, but by 16 hpf had detached sevenfold, with different schedules. Initially from most of the neural tube, the only remaining point (16–33 hpf), area increased but volume remained of attachment through the optic stalk. The vesicle constant; later (33–72 hpf) both increased. When sagged, so that its erstwhile dorsal and ventral sur- the volume remained constant, the presumptive faces faced laterally and medially, respectively, and the pigmented epithelium (PE) shrank and the pre- choroid fissure formed, but caudal to the optic stalk, sumptive neural retina (NR) enlarged.
    [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]
  • Semaphorin3a/Neuropilin-1 Signaling Acts As a Molecular Switch Regulating Neural Crest Migration During Cornea Development
    Developmental Biology 336 (2009) 257–265 Contents lists available at ScienceDirect Developmental Biology journal homepage: www.elsevier.com/developmentalbiology Semaphorin3A/neuropilin-1 signaling acts as a molecular switch regulating neural crest migration during cornea development Peter Y. Lwigale a,⁎, Marianne Bronner-Fraser b a Department of Biochemistry and Cell Biology, MS 140, Rice University, P.O. Box 1892, Houston, TX 77251, USA b Division of Biology, 139-74, California Institute of Technology, Pasadena, CA 91125, USA article info abstract Article history: Cranial neural crest cells migrate into the periocular region and later contribute to various ocular tissues Received for publication 2 April 2009 including the cornea, ciliary body and iris. After reaching the eye, they initially pause before migrating over Revised 11 September 2009 the lens to form the cornea. Interestingly, removal of the lens leads to premature invasion and abnormal Accepted 6 October 2009 differentiation of the cornea. In exploring the molecular mechanisms underlying this effect, we find that Available online 13 October 2009 semaphorin3A (Sema3A) is expressed in the lens placode and epithelium continuously throughout eye development. Interestingly, neuropilin-1 (Npn-1) is expressed by periocular neural crest but down- Keywords: Semaphorin3A regulated, in a manner independent of the lens, by the subpopulation that migrates into the eye and gives Neuropilin-1 rise to the cornea endothelium and stroma. In contrast, Npn-1 expressing neural crest cells remain in the Neural crest periocular region and contribute to the anterior uvea and ocular blood vessels. Introduction of a peptide that Cornea inhibits Sema3A/Npn-1 signaling results in premature entry of neural crest cells over the lens that Lens phenocopies lens ablation.
    [Show full text]
  • Telovelar Approach to the Fourth Ventricle: Microsurgical Anatomy
    J Neurosurg 92:812–823, 2000 Telovelar approach to the fourth ventricle: microsurgical anatomy ANTONIO C. M. MUSSI, M.D., AND ALBERT L. RHOTON, JR., M.D. Department of Neurological Surgery, University of Florida, Gainesville, Florida Object. In the past, access to the fourth ventricle was obtained by splitting the vermis or removing part of the cere- bellum. The purpose of this study was to examine the access to the fourth ventricle achieved by opening the tela cho- roidea and inferior medullary velum, the two thin sheets of tissue that form the lower half of the roof of the fourth ven- tricle, without incising or removing part of the cerebellum. Methods. Fifty formalin-fixed specimens, in which the arteries were perfused with red silicone and the veins with blue silicone, provided the material for this study. The dissections were performed in a stepwise manner to simulate the exposure that can be obtained by retracting the cerebellar tonsils and opening the tela choroidea and inferior medullary velum. Conclusions. Gently displacing the tonsils laterally exposes both the tela choroidea and the inferior medullary velum. Opening the tela provides access to the floor and body of the ventricle from the aqueduct to the obex. The additional opening of the velum provides access to the superior half of the roof of the ventricle, the fastigium, and the superolater- al recess. Elevating the tonsillar surface away from the posterolateral medulla exposes the tela, which covers the later- al recess, and opening this tela exposes the structure forming
    [Show full text]
  • Homocysteine Intensifies Embryonic LIM3 Expression in Migratory Neural Crest Cells: a Quantitative Confocal Microscope Study
    University of Northern Iowa UNI ScholarWorks Dissertations and Theses @ UNI Student Work 2014 Homocysteine intensifies embryonic LIM3 expression in migratory neural crest cells: A quantitative confocal microscope study Jordan Naumann University of Northern Iowa Let us know how access to this document benefits ouy Copyright ©2014 Jordan Naumann Follow this and additional works at: https://scholarworks.uni.edu/etd Part of the Biology Commons Recommended Citation Naumann, Jordan, "Homocysteine intensifies embryonic LIM3 expression in migratory neural crest cells: A quantitative confocal microscope study" (2014). Dissertations and Theses @ UNI. 89. https://scholarworks.uni.edu/etd/89 This Open Access Thesis is brought to you for free and open access by the Student Work at UNI ScholarWorks. It has been accepted for inclusion in Dissertations and Theses @ UNI by an authorized administrator of UNI ScholarWorks. For more information, please contact [email protected]. Copyright by JORDAN NAUMANN 2014 All Rights Reserved HOMOCYSTEINE INTENSIFIES EMBRYONIC LIM3 EXPRESSION IN MIGRATORY NEURAL CREST CELLS – A QUANTITATIVE CONFOCAL MICROSCOPE STUDY An Abstract of a Thesis Submitted in Partial Fulfillment of the Requirements for the Degree Master of Science Jordan Naumann University of Northern Iowa May 2014 ABSTRACT Elevated levels of homocysteine in maternal blood and amniotic fluid are associated with cardiovascular, renal, skeletal, and endocrine diseases and also with embryonic malformations related to neural crest cells. Neural crest cells are necessary for the formation of tissues and organs throughout the body of vertebrate animals. The migration of neural crest cells is essential for proper development of the target tissues. When migration is disrupted, abnormalities may occur.
    [Show full text]
  • Bilayered Optic Cup Is Defined Anatomically by The
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector 398 ABSTRACTS / Developmental Biology 295 (2006) 393–402 bilayered optic cup is defined anatomically by the presence of 198 the prospective neural retina (NR) in the distal layer and the Characterization of silica spicule formation during the retinal pigmented epithelium (RPE) proximally. Accordingly, resuscitation and in vitro cell culture of molecular markers accompany morphogenesis by restricting Hymeniacidon perleve their expression to definite compartments. For instance, in the Wei Zhang 1, Xupeng Cao 2, Xingju Yu 1 optic cup, the prospective neural retina expresses Chx10, and the 1 Marine Bioproducts Engineering Group, Dalian Institute of RPE, Mitf. However, to facilitate identification of definite events Chemical Physics, Chinese Academy of Sciences, during oculogenesis, there remains a need to identify additional Dalian, China markers of optical development. Thus, we performed here a 2 Graduate School of the Chinese Academy of Sciences, screen for Wnt ligands that are expressed during eye develop- Beijing, China ment. Specifically, we examined the expression of Wnt1, Wnt3, Wnt4-1 and Wnt5A during chick optic vesicles stages up to optic The biogenic silica mineralization in an intertidal marine cup formation. Of these four genes, only Wnt5A was consis- sponge Hymeniacidon perleve (Porifera: Demospongiae) has tently expressed in the dorsal optic cup. Although Wnt1, Wnt3 been investigated during the developmental process over one and Wnt4-1 were present in the developing nervous system, year period and in an in vitro sponge cell culture. Tissue neither was found in the optic vesicle or cup.
    [Show full text]
  • Early Neuronal and Glial Fate Restriction of Embryonic Neural Stem Cells
    The Journal of Neuroscience, March 5, 2008 • 28(10):2551–2562 • 2551 Development/Plasticity/Repair Early Neuronal and Glial Fate Restriction of Embryonic Neural Stem Cells Delphine Delaunay,1,2 Katharina Heydon,1,2 Ana Cumano,3 Markus H. Schwab,4 Jean-Le´on Thomas,1,2 Ueli Suter,5 Klaus-Armin Nave,4 Bernard Zalc,1,2 and Nathalie Spassky1,2 1Inserm, Unite´ 711, 75013 Paris, France, 2Institut Fe´de´ratif de Recherche 70, Faculte´deMe´decine, Universite´ Pierre et Marie Curie, 75013 Paris, France, 3Inserm, Unite´ 668, Institut Pasteur, 75724 Paris Cedex 15, France, 4Max-Planck-Institute of Experimental Medicine, D-37075 Goettingen, Germany, and 5Institute of Cell Biology, Swiss Federal Institute of Technology (ETH), ETH Ho¨nggerberg, CH-8093 Zu¨rich, Switzerland The question of how neurons and glial cells are generated during the development of the CNS has over time led to two alternative models: either neuroepithelial cells are capable of giving rise to neurons first and to glial cells at a later stage (switching model), or they are intrinsically committed to generate one or the other (segregating model). Using the developing diencephalon as a model and by selecting a subpopulation of ventricular cells, we analyzed both in vitro, using clonal analysis, and in vivo, using inducible Cre/loxP fate mapping, the fate of neuroepithelial and radial glial cells generated at different time points during embryonic development. We found that, during neurogenic periods [embryonic day 9.5 (E9.5) to 12.5], proteolipid protein ( plp)-expressing cells were lineage-restricted neuronal precursors, but later in embryogenesis, during gliogenic periods (E13.5 to early postnatal), plp-expressing cells were lineage-restricted glial precursors.
    [Show full text]
  • Stages of Embryonic Development of the Zebrafish
    DEVELOPMENTAL DYNAMICS 2032553’10 (1995) Stages of Embryonic Development of the Zebrafish CHARLES B. KIMMEL, WILLIAM W. BALLARD, SETH R. KIMMEL, BONNIE ULLMANN, AND THOMAS F. SCHILLING Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403-1254 (C.B.K., S.R.K., B.U., T.F.S.); Department of Biology, Dartmouth College, Hanover, NH 03755 (W.W.B.) ABSTRACT We describe a series of stages for Segmentation Period (10-24 h) 274 development of the embryo of the zebrafish, Danio (Brachydanio) rerio. We define seven broad peri- Pharyngula Period (24-48 h) 285 ods of embryogenesis-the zygote, cleavage, blas- Hatching Period (48-72 h) 298 tula, gastrula, segmentation, pharyngula, and hatching periods. These divisions highlight the Early Larval Period 303 changing spectrum of major developmental pro- Acknowledgments 303 cesses that occur during the first 3 days after fer- tilization, and we review some of what is known Glossary 303 about morphogenesis and other significant events that occur during each of the periods. Stages sub- References 309 divide the periods. Stages are named, not num- INTRODUCTION bered as in most other series, providing for flexi- A staging series is a tool that provides accuracy in bility and continued evolution of the staging series developmental studies. This is because different em- as we learn more about development in this spe- bryos, even together within a single clutch, develop at cies. The stages, and their names, are based on slightly different rates. We have seen asynchrony ap- morphological features, generally readily identi- pearing in the development of zebrafish, Danio fied by examination of the live embryo with the (Brachydanio) rerio, embryos fertilized simultaneously dissecting stereomicroscope.
    [Show full text]
  • Embryology, Anatomy, and Physiology of the Afferent Visual Pathway
    CHAPTER 1 Embryology, Anatomy, and Physiology of the Afferent Visual Pathway Joseph F. Rizzo III RETINA Physiology Embryology of the Eye and Retina Blood Supply Basic Anatomy and Physiology POSTGENICULATE VISUAL SENSORY PATHWAYS Overview of Retinal Outflow: Parallel Pathways Embryology OPTIC NERVE Anatomy of the Optic Radiations Embryology Blood Supply General Anatomy CORTICAL VISUAL AREAS Optic Nerve Blood Supply Cortical Area V1 Optic Nerve Sheaths Cortical Area V2 Optic Nerve Axons Cortical Areas V3 and V3A OPTIC CHIASM Dorsal and Ventral Visual Streams Embryology Cortical Area V5 Gross Anatomy of the Chiasm and Perichiasmal Region Cortical Area V4 Organization of Nerve Fibers within the Optic Chiasm Area TE Blood Supply Cortical Area V6 OPTIC TRACT OTHER CEREBRAL AREASCONTRIBUTING TO VISUAL LATERAL GENICULATE NUCLEUSPERCEPTION Anatomic and Functional Organization The brain devotes more cells and connections to vision lular, magnocellular, and koniocellular pathways—each of than any other sense or motor function. This chapter presents which contributes to visual processing at the primary visual an overview of the development, anatomy, and physiology cortex. Beyond the primary visual cortex, two streams of of this extremely complex but fascinating system. Of neces- information flow develop: the dorsal stream, primarily for sity, the subject matter is greatly abridged, although special detection of where objects are and for motion perception, attention is given to principles that relate to clinical neuro- and the ventral stream, primarily for detection of what ophthalmology. objects are (including their color, depth, and form). At Light initiates a cascade of cellular responses in the retina every level of the visual system, however, information that begins as a slow, graded response of the photoreceptors among these ‘‘parallel’’ pathways is shared by intercellular, and transforms into a volley of coordinated action potentials thalamic-cortical, and intercortical connections.
    [Show full text]
  • Drosophila Aurora-A Kinase Inhibits Neuroblast Self-Renewal by Regulating Apkc/Numb Cortical Polarity and Spindle Orientation
    Downloaded from genesdev.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation Cheng-Yu Lee,1,3,4 Ryan O. Andersen,1,3 Clemens Cabernard,1 Laurina Manning,1 Khoa D. Tran,1 Marcus J. Lanskey,1 Arash Bashirullah,2 and Chris Q. Doe1,5 1Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, Oregon 97403, USA; 2Department of Human Genetics, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA Regulation of stem cell self-renewal versus differentiation is critical for embryonic development and adult tissue homeostasis. Drosophila larval neuroblasts divide asymmetrically to self-renew, and are a model system for studying stem cell self-renewal. Here we identify three mutations showing increased brain neuroblast numbers that map to the aurora-A gene, which encodes a conserved kinase implicated in human cancer. Clonal analysis and time-lapse imaging in aurora-A mutants show single neuroblasts generate multiple neuroblasts (ectopic self-renewal). This phenotype is due to two independent neuroblast defects: abnormal atypical protein kinase C (aPKC)/Numb cortical polarity and failure to align the mitotic spindle with the cortical polarity axis. numb mutant clones have ectopic neuroblasts, and Numb overexpression partially suppresses aurora-A neuroblast overgrowth (but not spindle misalignment). Conversely, mutations that disrupt spindle alignment but not cortical polarity have increased neuroblasts. We conclude that Aurora-A and Numb are novel inhibitors of neuroblast self-renewal and that spindle orientation regulates neuroblast self-renewal.
    [Show full text]
  • Bmps and Ventral Optic Cup Differentiation 3163
    Development 129, 3161-3171 (2002) 3161 Printed in Great Britain © The Company of Biologists Limited 2002 DEV1795 The role of bone morphogenetic proteins in the differentiation of the ventral optic cup Ruben Adler1 and Teri L. Belecky-Adams2,* 1The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA 2Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA *Author for correspondence (e-mail: [email protected]) Accepted 20 March 2002 SUMMARY The ventral region of the chick embryo optic cup undergoes stages of development, this treatment resulted in a complex process of differentiation leading to the microphthalmia with concomitant disruption of the formation of four different structures: the neural retina, developing neural retina, RPE and lens. At optic cup the retinal pigment epithelium (RPE), the optic disk/optic stages, however, noggin overexpression caused colobomas, stalk, and the pecten oculi. Signaling molecules such as pecten agenesis, replacement of the ventral RPE by retinoic acid and sonic hedgehog have been implicated neuroepithelium-like tissue, and ectopic expression of optic in the regulation of these phenomena. We have now stalk markers in the region of the ventral retina and RPE. investigated whether the bone morphogenetic proteins This was frequently accompanied by abnormal growth of (BMPs) also regulate ventral optic cup development. Loss- ganglion cell axons, which failed to enter the optic nerve. of-function experiments were carried out in chick embryos The data suggest that endogenous BMPs have significant in ovo, by intraocular overexpression of noggin, a protein effects on the development of ventral optic cup structures. that binds several BMPs and prevents their interactions with their cognate cell surface receptors.
    [Show full text]
  • Molecular Regulation of Visual System Development: More Than Meets the Eye
    Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Molecular regulation of visual system development: more than meets the eye Takayuki Harada,1,2 Chikako Harada,1,2 and Luis F. Parada1,3 1Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA; 2Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan Vertebrate eye development has been an excellent model toderm, intercalating mesoderm, surface ectoderm, and system to investigate basic concepts of developmental neural crest (Fig. 1). The neuroectoderm differentiates biology ranging from mechanisms of tissue induction to into the retina, iris, and optic nerve; the surface ecto- the complex patterning and bidimensional orientation of derm gives rise to lens and corneal epithelium; the me- the highly specialized retina. Recent advances have shed soderm differentiates into the extraocular muscles and light on the interplay between numerous transcriptional the fibrous and vascular coats of the eye; and neural crest networks and growth factors that are involved in the cells become the corneal stroma sclera and corneal en- specific stages of retinogenesis, optic nerve formation, dothelium. The vertebrate eye originates from bilateral and topographic mapping. In this review, we summarize telencephalic optic grooves. In humans, optic vesicles this recent progress on the molecular mechanisms un- emerge at the end of the fourth week of development and derlying the development of the eye, visual system, and soon thereafter contact the surface ectoderm to induce embryonic tumors that arise in the optic system.
    [Show full text]