DOCSLIB.ORG

Title of Dissertation Goes Here in All Caps

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Title of Dissertation Goes Here in All Caps GENOME-WIDE ANALYSIS OF TRANSCRIPTION FACTORS ASCL1 AND PTF1A IN DEVELOPMENT AND CANCER APPROVED BY SUPERVISORY COMMITTEE Jane E. Johnson, Ph.D. Gang. Yu, Ph.D. Q. Richard Lu, Ph.D. Tae-Kyung Kim, Ph.D. DEDICATION I dedicate this to my mother and wife, for their love and devotion, and their endless support throughout my life. GENOME-WIDE ANALYSIS OF TRANSCRIPTION FACTORS ASCL1 AND PTF1A IN DEVELOPMENT AND CANCER by MARK DOMINIC BORROMEO DISSERTATION Presented to the Faculty of the Graduate School of Biomedical Sciences The University of Texas Southwestern Medical Center at Dallas In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY The University of Texas Southwestern Medical Center at Dallas Dallas, Texas December, 2013 Copyright by Mark Dominic Borromeo, 2013 All Rights Reserved GENOME-WIDE ANALYSIS OF TRANSCRIPTION FACTORS ASCL1 AND PTF1A IN DEVELOPMENT AND CANCER Mark Dominic Borromeo, Ph.D. The University of Texas Southwestern Medical Center at Dallas, 2013 Jane E. Johnson, Ph.D. Cell fate specification in the developing embryo relies on combinations of transcription factors to regulate tissue specific gene programs. Many of the same transcription factors can be found in multiple tissue types and are crucial for their development, and at other times these same factors can be misused in disease states. The basic helix-loop-helix (bHLH) factors Ascl1 and Ptf1a are examples of factors that give rise to and function in multiple tissues. Ascl1 and Ptf1a are essential for generating the correct number and sub-type of neurons in multiple regions of the nervous system. In addition, Ptf1a is required in the developing pancreas for both its formation and maturation, while Ascl1 is crucial for tumor v growth in malignant small cell lung carcinoma (SCLC). It is unknown if Ascl1 and Ptf1a directly regulate different genes programs in these disparate tissues. Furthermore, Ptf1a and Ascl1 are members of same transcription factor family, which recognize and bind a similar DNA sequence. How these two factors achieve specificity of DNA binding and gene target selection in vivo is unknown. These questions have long been unanswered due in part to the lack of known direct transcriptional targets. Thus, to understand how Ascl1 and Ptf1a function in these processes, the direct transcriptional targets were identified genome-wide in the multiple tissues using ChIP-Seq and RNA-Seq. Overwhelmingly, Ascl1 and Ptf1a directly regulate different gene programs important for each tissue. Within a given tissue, the specificity of Ascl1 and Ptf1a function is partly explained by their differences in E-box sequence preferences. Ptf1a and Ascl1 are co-expressed in a subset of cells in the dorsal neural tube, and comparative analysis of their binding sites show that they bind a common E- box. However, Ptf1a can also bind a distinct E-box, which is found enriched in binding sites unique to Ptf1a. However, analysis of Ascl1 binding in SCLC and Ptf1a binding in the developing pancreas, shows that their E-box preferences change and does not reflect the same type of E-box they bind in the neural tube. Mechanisms in addition to E-box specificity are likely in use because tissue specific binding coincides with tissue-specific chromatin accessibility and enrichment of lineage-specific transcription factor binding motifs. Thus, Ascl1 and Ptf1a make use of different tissue-specific co-factors to regulate tissue-specific genes. This study provides insights into how a single factor can regulate the transcription of different genes in different tissue types, and how two related E-box binding proteins regulate distinct genes. ACKNOWLEDGEMENT This dissertation would not have been possible without the support and guidance from my friends, family, and colleagues. I would like to acknowledge my mentor Dr. Jane Johnson, for her endless support and guidance throughout my graduate school career. Because of Dr. Johnson’s patience and dedication towards teaching her students, I feel prepared to take on any challenge that I may face during my next phase of my scientific career. I have learned through Dr. Johnson that there is no shortcut or substitute for good quality of work, and that good work will always earn the highest respect and appreciation from your colleagues. I would like to thank the members of my dissertation committee: Drs. Gang Yu, Richard Lu, and Tae-Kyung Kim. Together they have provided me with both technical and biological insight that was crucial for the success of my projects. I was privileged to work with so many talented scientists on several different projects and I would like to thank all of them for sharing their knowledge and assisting me at the lab bench. I would specially like to thank members of the Ray MacDonald, John Minna, and Francois Guillemot Labs. Finally, I would like to give special thanks to all the past and present members of the Jane Johnson lab. I was blessed to be surrounded by so many gifted scientists that were willing to pass their knowledge on to me. Without their training and helpful discussion I would not have succeeded. vii TABLE OF CONTENTS DEDICATION ....................................................................................................... II ABSTRACT ........................................................................................................... V ACKNOWLEDGEMENT .................................................................................. VII TABLE OF CONTENTS ................................................................................... VIII PRIOR PUBLICATIONS .................................................................................... XI LIST OF FIGURES ............................................................................................ XII LIST OF APPENDIX ......................................................................................... XV LIST OF ABBREVIATIONS ............................................................................ XVI KEY WORDS .................................................................................................. XVII CHAPTER ONE ..................................................................................................................... 1 INTRODUCTION ................................................................................................................ 1 Tissue-specific gene regulation through cis-regulatory elements ..................................... 1 Sequence specific binding of transcription factors ........................................................... 4 Class II bHLH transcription factors bind a degenerate E-box sequence ......................... 6 Tissue-specific bHLH and HD factors specify somatosensory neurons in the dorsal spinal cord ......................................................................................................................... 7 Ascl1 and Ptf1a have opposing roles in neuronal subtype specification in the dorsal spinal cord ......................................................................................................................... 8 Ptf1a and Ascl1 give rise to multiple tissue types outside the neural tube ..................... 10 Ptf1a specifies GABAergic neurons in multiple regions of the nervous system and is also require for pancreas development ........................................................................... 11 Ptf1a forms a trimeric complex with E-protein and Rbpj to activate transcription ........ 12 Direct Transcriptional Targets of Ptf1a .......................................................................... 13 Ascl1 has neurogenic, oncogenic and gliogenic functions in the nervous system ......... 13 Transcriptional Targets of Ascl1 .................................................................................... 15 THESIS RATIONALE AND GOALS ............................................................................... 15 CHAPTER TWO .................................................................................................................. 21 Transcription Factor Network Specifying Inhibitory versus Excitatory Neurons in the Dorsal Spinal Cord ............................................................................................................... 21 INTRODUCTION .............................................................................................................. 21 MATERIALS AND METHODS ........................................................................................ 23 RESULTS ........................................................................................................................... 28 Ascl1 and Ptf1a bind largely distinct sites within neural tube chromatin and have distinct E-box sequence preferences ............................................................................... 28 Enrichment of non-E-box transcription factor motifs within Ascl1 and Ptf1a bound genomic regions .............................................................................................................. 30 Ascl1 and Ptf1a have opposite actions in neuronal subtype specification...................... 32 Homeodomain neuronal specification factors are direct downstream targets of Ascl1 and Ptf1a ................................................................................................................................ 35 Ascl1 directly regulates genes involved in multiple processes of neurogenesis ............ 38 Ptf1a directly represses the glutamatergic fate and
Load more

Recommended publications
  • Endocrinology
    Endocrinology INTRODUCTION Endocrinology 1. Endocrinology is the study of the endocrine system secretions and their role at target cells within the body and nervous system are the major contributors to the flow of information between different cells and tissues. 2. Two systems maintain Homeostasis a. b 3. Maintain a complicated relationship 4. Hormones 1. The endocrine system uses hormones (chemical messengers/neurotransmitters) to convey information between different tissues. 2. Transport via the bloodstream to target cells within the body. It is here they bind to receptors on the cell surface. 3. Non-nutritive Endocrine System- Consists of a variety of glands working together. 1. Paracrine Effect (CHEMICAL) Endocrinology Spring 2013 Page 1 a. Autocrine Effect i. Hormones released by cells that act on the membrane receptor ii. When a hormone is released by a cell and acts on the receptors located WITHIN the same cell. Endocrine Secretions: 1. Secretions secreted Exocrine Secretion: 1. Secretion which come from a gland 2. The secretion will be released into a specific location Nervous System vs tHe Endocrine System 1. Nervous System a. Neurons b. Homeostatic control of the body achieved in conjunction with the endocrine system c. Maintain d. This system will have direct contact with the cells to be affected e. Composed of both the somatic and autonomic systems (sympathetic and parasympathetic) Endocrinology Spring 2013 Page 2 2. Endocrine System a. b. c. 3. Neuroendocrine: a. These are specialized neurons that release chemicals that travel through the vascular system and interact with target tissue. b. Hypothalamus à posterior pituitary gland History of tHe Endocrine System Bertold (1849)-FATHER OF ENDOCRINOLOGY 1.
    [Show full text]
  • Segregating Expression Domains of Two Goosecoid Genes During the Transition from Gastrulation to Neurulation in Chick Embryos
    Development 124, 1443-1452 (1997) 1443 Printed in Great Britain © The Company of Biologists Limited 1997 DEV2146 Segregating expression domains of two goosecoid genes during the transition from gastrulation to neurulation in chick embryos Lydia Lemaire1, Tobias Roeser1, Juan Carlos Izpisúa-Belmonte2 and Michael Kessel1,* 1Max-Planck-Institut für biophysikalische Chemie, Am Fassberg, D-37077 Göttingen, Germany 2The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA *Author for correspondence (e-mail: [email protected]) SUMMARY We report the isolation and characterization of a chicken plate around the anterior streak and overlying the pre- gene, GSX, containing a homeobox similar to that of the chordal plate. We demonstrate that the GSX-positive part goosecoid gene. The structure of the GSX gene and the of the primitive streak induces gastrulation, while the GSC- deduced GSX protein are highly related to the previously expressing part induces neurulation. After full extension of described goosecoid gene. The two homeodomains are 74% the streak, the fate of cells now characterized by GSX is to identical. In the first few hours of chick embryogenesis, the undergo neurulation, while those expressing GSC undergo expression pattern of GSX is similar to GSC, in the gastrulation. We discuss the effect of a duplicated basic posterior margin of the embryo and the young primitive goosecoid identity for the generation of a chordate nervous streak. Later during gastrulation, expression of the two system in ontogeny and phylogeny. genes segregate. GSC is expressed in the anterior part of the primitive streak, then in the node, and finally in the pre- chordal plate.
    [Show full text]
  • Breakup of a Homeobox Cluster After Genome Duplication in Teleosts
    Breakup of a homeobox cluster after genome duplication in teleosts John F. Mulley*, Chi-hua Chiu†, and Peter W. H. Holland*‡ *Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, United Kingdom; and †Rutgers University, Department of Genetics, Life Sciences Building, Piscataway, NJ 08854 Edited by Eric H. Davidson, California Institute of Technology, Pasadena, CA, and approved May 11, 2006 (received for review January 13, 2006) Several families of homeobox genes are arranged in genomic been active throughout vertebrate history, we show that in the clusters in metazoan genomes, including the Hox, ParaHox, NK, ray-finned fish clade, the ParaHox gene cluster was lost in the Rhox, and Iroquois gene clusters. The selective pressures respon- evolution of teleosts after divergence from more basal ray- sible for maintenance of these gene clusters are poorly under- finned fish. stood. The ParaHox gene cluster is evolutionarily conserved be- tween amphioxus and human but is fragmented in teleost fishes. Results We show that two basal ray-finned fish, Polypterus and Amia, each We searched the emerging genome sequences of zebrafish possess an intact ParaHox cluster; this implies that the selective (Danio rerio; www.sanger.ac.uk͞Projects͞D࿝rerio) and two pressure maintaining clustering was lost after whole-genome pufferfish [Tetraodon nigroviridis (10) and Takifugu rubripes duplication in teleosts. Cluster breakup is because of gene loss, not (11)] for DNA sequences assignable to the Gsx, Xlox, and Cdx transposition or inversion, and the total number of ParaHox genes gene families. Comparison between species gave a consistent is the same in teleosts, human, mouse, and frog.
    [Show full text]
  • Septal Contributions to Olfactory Bulb Interneuron Diversity in the Embryonic Mouse Telencephalon: Role of the Homeobox Gene Gsx2 Shenyue Qin1,2, Stephanie M
    Qin et al. Neural Development (2017) 12:13 DOI 10.1186/s13064-017-0090-5 RESEARCH ARTICLE Open Access Septal contributions to olfactory bulb interneuron diversity in the embryonic mouse telencephalon: role of the homeobox gene Gsx2 Shenyue Qin1,2, Stephanie M. Ware5, Ronald R. Waclaw1,4 and Kenneth Campbell1,3* Abstract Background: Olfactory bulb (OB) interneurons are known to represent diverse neuronal subtypes, which are thought to originate from a number of telencephalic regions including the embryonic dorsal lateral ganglionic eminence (dLGE) and septum. These cells migrate rostrally toward the OB, where they then radially migrate to populate different OB layers including the granule cell layer (GCL) and the outer glomerular layer (GL). Although previous studies have attempted to investigate regional contributions to OB interneuron diversity, few genetic tools have been used to address this question at embryonic time points when the earliest populations are specified. Methods: In this study, we utilized Zic3-lacZ and Gsx2e-CIE transgenic mice as genetic fate-mapping tools to study OB interneuron contributions derived from septum and LGE, respectively. Moreover, to address the regional (i.e. septal) requirements of the homeobox gene Gsx2 for OB interneuron diversity, we conditionally inactivated Gsx2 in the septum, leaving it largely intact in the dLGE, by recombining the Gsx2 floxed allele using Olig2Cre/+ mice. Results: Our fate mapping studies demonstrated that the dLGE and septum gave rise to OB interneuron subtypes differently. Notably, the embryonic septum was found to give rise largely to the calretinin+ (CR+) GL subtype, while the dLGE was more diverse, generating all major GL subpopulations as well as many GCL interneurons.
    [Show full text]
  • Early Transcriptional Targets of Myod Link Myogenesis and Somitogenesis
    Developmental Biology 371 (2012) 256–268 Contents lists available at SciVerse ScienceDirect Developmental Biology journal homepage: www.elsevier.com/locate/developmentalbiology Early transcriptional targets of MyoD link myogenesis and somitogenesis Richard J. Maguire, Harry V. Isaacs, Mary Elizabeth Pownall n Biology Department, University of York, Heslington, York, North Yorkshire YO10 5YW, United Kingdom article info abstract Article history: In order to identify early transcriptional targets of MyoD prior to skeletal muscle differentiation, we Received 27 February 2012 have undertaken a transcriptomic analysis on gastrula stage Xenopus embryos in which MyoD has been Received in revised form knocked-down. Our validated list of genes transcriptionally regulated by MyoD includes Esr1 and Esr2, 10 July 2012 which are known targets of Notch signalling, and Tbx6, mesogenin, and FoxC1; these genes are all are Accepted 22 August 2012 known to be essential for normal somitogenesis but are expressed surprisingly early in the mesoderm. Available online 31 August 2012 In addition we found that MyoD is required for the expression of myf5 in the early mesoderm, in Keywords: contrast to the reverse relationship of these two regulators in amniote somites. These data highlight a Skeletal muscle role for MyoD in the early mesoderm in regulating a set of genes that are essential for both myogenesis Gene regulation and somitogenesis. Muscle progenitors & 2012 Elsevier Inc. All rights reserved. Determination Introduction gastrula embryo requires continued cell signals, such as FGF4, to maintain a myogenic fate (Standley et al., 2001), however, a single In vertebrates, the myogenic regulatory genes myoD, myf5, cell taken from a late gastrula embryo behaves as a determined myogenin, and mrf4 code for bHLH transcription factors which are myoblast: when transplanted to a ventral region, it differentiates expressed specifically in the myogenic cell lineage.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,377,886 B2 Susztak Et Al
    US008377886B2 (12) United States Patent (10) Patent No.: US 8,377,886 B2 Susztak et al. (45) Date of Patent: Feb. 19, 2013 (54) USE OF GAMMA SECRETASE INHIBITORS 7,144.910 B2 12/2006 Madin et al. AND NOTCH PATHWAY INHIBITORS FOR E.R. 358 (SR." TREATMENT AND PREVENTION OF RENAL 2003/0166894 A1* 9/2003 Kapeller Libermann et al. .......... 536,231 DISEASE 2006/0264380 A1* 11/2006 Hellstrom et al. .............. 514, 19 2007/0066568 A1 3/2007 Dalton et al. (75) Inventors: Katalin Susztak, Cresskill, NJ (US); Bernhard Bielesz, Rye, NY (US); FOREIGN PATENT DOCUMENTS Thiruvur G. Niranjan, Bronx, NY (US) WO WO2004/073630 * 9/2004 (73) Assignee: Albert Einstein College of Medicine of OTHER PUBLICATIONS Yeshiva University, Bronx, NY (US) “Glomerulonephritis' (in WWW. intellihealth.com/ IH/ht?t=31198& p=~br, IHWI-st, 24479-r, WSIH (*) Notice: Subject to any disclaimer, the term of this W000-b.* liprevent).* patent is extended or adjusted under 35 Vanes et al. in Nature 435(16), pp. 959-963 (2005).* U.S.C. 154(b) by 78 days. Masuda et al. in American Journal of Pathology, 159(2) (2001).* Yum et al. in Human Pathology 15(10), 921-927 (1984).* PCT International Preliminary Report on Patentability (dated Mar. (21) Appl. No.: 12/733,339 16, 2010) in connection with PCT International Patent Application No. PCT/US2003/010362, 6 pages. (22) PCT Filed: Sep. 4, 2008 Cheng HT et al., entitled Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron, Development (86) PCT NO.: PCT/US2O08/O10362 134,801-811 (2007).
    [Show full text]
  • Molecular Control of Neurogenesis: Aview from the Mammalian Cerebral Cortex
    Downloaded from http://cshperspectives.cshlp.org/ on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press Molecular Control of Neurogenesis: AView from the Mammalian Cerebral Cortex Ben Martynoga, Daniela Drechsel, and Franc¸ois Guillemot Division of Molecular Neurobiology, National Institute for Medical Research, Mill Hill, London NW71AA, United Kingdom Correspondence: [email protected] SUMMARY The mammalian nervous system is the most complex organ of any living organism. How this complexity is generated during neural development is just beginning to be elucidated. This article discusses the signaling, transcriptional, and epigenetic mechanisms that are involved in neural development. The first part focuses on molecules that control neuronal numbers through regulation of the timing of onset of neurogenesis, the timing of the neuronal-to-glial switch, and the rate of progenitor proliferation. The second part focuses on molecules that control neuronal diversity by generating spatially or temporally distinct populations of neuro- nal progenitors. Most of the studies discussed in this article are focused on the developing mammalian cerebral cortex, because this is one of the main model systems for neural devel- opmental studies and many of the mechanisms identified in this tissue also operate elsewhere in the developing brain and spinal cord. Outline 1 Introduction 4 Concluding remarks 2 Controlling neuronal number References in the embryonic brain 3 Generating neuronal diversity in the embryonic brain Editors: Patrick P.L. Tam, W. James Nelson, and Janet Rossant Additional Perspectives on Mammalian Development available at www.cshperspectives.org Copyright # 2012 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a008359 Cite this article as Cold Spring Harb Perspect Biol 2012;4:a008359 1 Downloaded from http://cshperspectives.cshlp.org/ on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press B.
    [Show full text]
  • BMC Biology Biomed Central
    BMC Biology BioMed Central Research article Open Access Classification and nomenclature of all human homeobox genes PeterWHHolland*†1, H Anne F Booth†1 and Elspeth A Bruford2 Address: 1Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK and 2HUGO Gene Nomenclature Committee, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK Email: Peter WH Holland* - [email protected]; H Anne F Booth - [email protected]; Elspeth A Bruford - [email protected] * Corresponding author †Equal contributors Published: 26 October 2007 Received: 30 March 2007 Accepted: 26 October 2007 BMC Biology 2007, 5:47 doi:10.1186/1741-7007-5-47 This article is available from: http://www.biomedcentral.com/1741-7007/5/47 © 2007 Holland et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described. Results: We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes.
    [Show full text]
  • ABC Transporters in Cancer Stem Cells: Beyond Chemoresistance
    International Journal of Molecular Sciences Review ABC Transporters in Cancer Stem Cells: Beyond Chemoresistance Romana-Rea Begicevic and Marco Falasca * ID Metabolic Signalling Group, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth WA 6102, Australia; [email protected] * Correspondence: [email protected]; Tel.: +61-08-9266-9712 Received: 16 October 2017; Accepted: 2 November 2017; Published: 8 November 2017 Abstract: The efficacy of chemotherapy is one of the main challenges in cancer treatment and one of the major obstacles to overcome in achieving lasting remission and a definitive cure in patients with cancer is the emergence of cancer resistance. Indeed, drug resistance is ultimately accountable for poor treatment outcomes and tumour relapse. There are various molecular mechanisms involved in multidrug resistance, such as the change in the activity of membrane transporters primarily belonging to the ATP binding cassette (ABC) transporter family. In addition, it has been proposed that this common feature could be attributed to a subpopulation of slow-cycling cancer stem cells (CSCs), endowed with enhanced tumorigenic potential and multidrug resistance. CSCs are characterized by the overexpression of specific surface markers that vary in different cancer cell types. Overexpression of ABC transporters has been reported in several cancers and more predominantly in CSCs. While the major focus on the role played by ABC transporters in cancer is polarized by their involvement in chemoresistance, emerging evidence supports a more active role of these proteins, in which they release specific bioactive molecules in the extracellular milieu. This review will outline our current understanding of the role played by ABC transporters in CSCs, how their expression is regulated and how they support the malignant metabolic phenotype.
    [Show full text]
  • Molecular Control of Development in the Reef Coral, Acropora Millepora
    Proceedings 9th International Coral Reef Symposium, Bali, Indonesia 23-27 October 2000 Molecular control of development in the reef coral, Acropora millepora E. E. Ball1, D. C. Hayward1, J. Catmull1,2, J. S. Reece-Hoyes1,2, N. R. Hislop1,2, P. L. Harrison3 and D. J. Miller2 ABSTRACT A brief overview of the embryonic and larval development of Acropora, including some previously unpublished data, provides the background for this review of our rapidly expanding knowledge of the genes that control early development in corals, with particular emphasis on Hox and Hox-like genes. Since the Phylum Cnidaria is widely accepted to be an ancient group of organisms, genes, and motifs within genes, that are shared by corals and higher metazoans are presumably ancient. Thus, shared genes allow us to study how gene structure and function have changed with time, while genes specific to higher metazoans have, presumably, evolved more recently. Anatomically, corals have many fewer cell types than higher metazoans, but it is not clear that this apparent simplicity will be reflected at the molecular level. We have already found Acropora representatives of structural genes, housekeeping genes, nuclear receptors, Hox-like genes, Pax genes and components of the dpp signalling pathway. However, thus far there is no unequivocal evidence for the cluster of Hox genes, known as the zootype genes, that is otherwise widespread among the Metazoa. As more data become available, the Cnidaria are making an increasing contribution to our knowledge of the evolution of gene structure, function, and regulation. We here illustrate the evolutionary approach that we are taking to the characterisation of coral genes with a review of our work on the Acropora Hox-like gene, cnox2-Am.
    [Show full text]
  • Safety Manual for Tms320f28002x User's Guide
    www.ti.com Table of Contents Functional Safety Information Safety Manual for TMS320F28002x ABSTRACT This document is a safety manual for the Texas Instruments TMS320F28002x safety critical real time microcontroller product family. The product family utilizes a common safety architecture that is implemented in multiple application-focused products. Table of Contents 1 Introduction.............................................................................................................................................................................3 2 TMS320F28002x Product Safety Capability and Constraints............................................................................................. 4 3 TI Development Process for Management of Systematic Faults....................................................................................... 4 3.1 TI New-Product Development Process.............................................................................................................................. 4 3.2 TI Safety Development Process.........................................................................................................................................5 4 TMS320F28002x Product Overview...................................................................................................................................... 7 4.1 C2000 Architecture and Product Overview........................................................................................................................ 7 4.2 Functional Safety Concept................................................................................................................................................
    [Show full text]
  • Viewed in [42])
    Wollesen et al. EvoDevo (2015) 6:41 DOI 10.1186/s13227-015-0037-z EvoDevo RESEARCH Open Access The ParaHox gene Gsx patterns the apical organ and central nervous system but not the foregut in scaphopod and cephalopod mollusks Tim Wollesen1*, Sonia Victoria Rodríguez Monje1, Carmel McDougall2, Bernard M. Degnan2 and Andreas Wanninger1 Abstract Background: It has been hypothesized that the ParaHox gene Gsx patterned the foregut of the last common bilate- rian ancestor. This notion was corroborated by Gsx expression in three out of four lophotrochozoan species, several ecdysozoans, and some deuterostomes. Remarkably, Gsx is also expressed in the bilaterian anterior-most central nervous system (CNS) and the gastropod and annelid apical organ. To infer whether these findings are consistent with other mollusks or even lophotrochozoans, we investigated Gsx expression in developmental stages of representatives of two other molluscan classes, the scaphopod Antalis entalis and the cephalopod Idiosepius notoides. Results: Gsx is not expressed in the developing digestive tract of Antalis entalis and Idiosepius notoides. Instead, it is expressed in cells of the apical organ in the scaphopod trochophore and in two cells adjacent to this organ. Late- stage trochophores express Aen-Gsx in cells of the developing cerebral and pedal ganglia and in cells close to the pavilion, mantle, and foot. In postmetamorphic specimens, Aen-Gsx is expressed in the cerebral and pedal ganglia, the foot, and the nascent captacula. In early squid embryos, Ino-Gsx is expressed in the cerebral, palliovisceral, and optic ganglia. In late-stage embryos, Ino-Gsx is additionally expressed close to the eyes and in the supraesophageal and posterior subesophageal masses and optic lobes.
    [Show full text]