Tinkering and the Origins of Heritable Anatomical Variation in Vertebrates
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Functional Analysis of the Homeobox Gene Tur-2 During Mouse Embryogenesis
Functional Analysis of The Homeobox Gene Tur-2 During Mouse Embryogenesis Shao Jun Tang A thesis submitted in conformity with the requirements for the Degree of Doctor of Philosophy Graduate Department of Molecular and Medical Genetics University of Toronto March, 1998 Copyright by Shao Jun Tang (1998) National Library Bibriothèque nationale du Canada Acquisitions and Acquisitions et Bibiiographic Services seMces bibliographiques 395 Wellington Street 395, rue Weifington OtbawaON K1AW OttawaON KYAON4 Canada Canada The author has granted a non- L'auteur a accordé une licence non exclusive licence alIowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distri%uteor sell reproduire, prêter' distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/nlm, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fkom it Ni la thèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. Functional Analysis of The Homeobox Gene TLr-2 During Mouse Embryogenesis Doctor of Philosophy (1998) Shao Jun Tang Graduate Department of Moiecular and Medicd Genetics University of Toronto Abstract This thesis describes the clonhg of the TLx-2 homeobox gene, the determination of its developmental expression, the characterization of its fiuiction in mouse mesodem and penpheral nervous system (PNS) developrnent, the regulation of nx-2 expression in the early mouse embryo by BMP signalling, and the modulation of the function of nX-2 protein by the 14-3-3 signalling protein during neural development. -
Role of Hox Genes in Regulating Digit Patterning ROCÍO PÉREZ-GÓMEZ, ENDIKA HARO, MARC FERNÁNDEZ-GUERRERO, MARÍA F
Int. J. Dev. Biol. 62: 797-805 (2018) https://doi.org/10.1387/ijdb.180200mr www.intjdevbiol.com Role of Hox genes in regulating digit patterning ROCÍO PÉREZ-GÓMEZ, ENDIKA HARO, MARC FERNÁNDEZ-GUERRERO, MARÍA F. BASTIDA and MARÍA A. ROS* Instituto de Biomedicina y Biotecnología de Cantabria, CSIC–SODERCAN Universidad de Cantabria, Santander, Spain ABSTRACT The distal part of the tetrapod limb, the autopod, is characterized by the presence of digits. The digits display a wide diversity of shapes and number reflecting selection pressure for functional adaptation. Despite extensive study, the different aspects of digit patterning, as well as the factors and mechanisms involved are not completely understood. Here, we review the evidence implicating Hox proteins in digit patterning and the interaction between Hox genes and the Sonic hedgehog/Gli3 pathway, the other major regulator of digit number and identity. Currently, it is well accepted that a self-organizing Turing-type mechanism underlies digit patterning, this being understood as the establishment of an iterative arrangement of digit/interdigit in the hand plate. We also discuss the involvement of 5’ Hox genes in regulating digit spacing in the digital plate and therefore the number of digits formed in this self-organizing system. KEY WORDS: limb development, Hox gene, digit patterning, Shh, Gli3 Introduction and Meyer, 2015). The digits are crucial elements for the function of the limb. They The basic plan of the tetrapod limb includes three distinct can be viewed as serial identical structures arranged along the proximo-distal (PD) segments: the stylopod (arm), the zeugopod antero-posterior (AP) axis of the autopod, thumb to little finger, or (forearm) and the autopod (hand/foot). -
Gabriel Dover)
Dear Mr Darwin (Gabriel Dover) Home | Intro | About | Feedback | Prev | Next | Search Steele: Lamarck's Was Signature Darwin Wrong? Molecular Drive: the Third Force in evolution Geneticist Gabriel Dover claims that there is a third force in evolution: 'Molecular Drive' beside natural selection and neutral drift. Molecular drive is operationally distinct from natural selection and neutral drift. According to Dover it explains biological phenomena, such as the 700 copies of a ribosomal RNA gene and the origin of the 173 legs of the centipede, which natural selection and neutral drift alone cannot explain. by Gert Korthof version 1.3 24 Mar 2001 Were Darwin and Mendel both wrong? Molecular Drive is, according to Dover, an important factor in evolution, because it shapes the genomes and forms of organisms. Therefore Neo-Darwinism is incomplete without Molecular Drive. It is no wonder that the spread of novel genes was ascribed to natural selection, because it was the only known process that could promote the spread of novel genes. Dover doesn't reject the existence of natural selection but points out cases where natural selection clearly fails as a mechanism. Molecular drive is a non-Darwinian mechanism because it is independent of selection. We certainly need forces in evolution, since natural selection itself is not a force. It is the passive outcome of other processes. It is not an active process, notwithstanding its name. Natural selection as an explanation is too powerful for its own good. Molecular drive is non-Mendelian because some DNA segments are multiplied disproportional. In Mendelian genetics genes are present in just two copies (one on the maternal and one on the paternal chromosome). -
Homeobox Gene Expression Profile in Human Hematopoietic Multipotent
Leukemia (2003) 17, 1157–1163 & 2003 Nature Publishing Group All rights reserved 0887-6924/03 $25.00 www.nature.com/leu Homeobox gene expression profile in human hematopoietic multipotent stem cells and T-cell progenitors: implications for human T-cell development T Taghon1, K Thys1, M De Smedt1, F Weerkamp2, FJT Staal2, J Plum1 and G Leclercq1 1Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium; and 2Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands Class I homeobox (HOX) genes comprise a large family of implicated in this transformation proces.14 The HOX-C locus transcription factors that have been implicated in normal and has been primarily implicated in lymphomas.15 malignant hematopoiesis. However, data on their expression or function during T-cell development is limited. Using degener- Hematopoietic cells are derived from stem cells that reside in ated RT-PCR and Affymetrix microarray analysis, we analyzed fetal liver (FL) in the embryo and in the adult bone marrow the expression pattern of this gene family in human multipotent (ABM), which have the unique ability to self-renew and thereby stem cells from fetal liver (FL) and adult bone marrow (ABM), provide a life-long supply of blood cells. T lymphocytes are a and in T-cell progenitors from child thymus. We show that FL specific type of hematopoietic cells that play a major role in the and ABM stem cells are similar in terms of HOX gene immune system. They develop through a well-defined order of expression, but significant differences were observed between differentiation steps in the thymus.16 Several transcription these two cell types and child thymocytes. -
Products for Morphogen Research
R&D Systems Tools for Cell Biology Research™ Products for Morphogen Research BMP-4 NEURAL PLATE BMP-7 PROSPECTIVE NEURAL CREST NON-NEURAL ECTODERM Noggin Shh Noggin PRESOMITIC MESODERM NOTOCHORD NON-NEURAL ECTODERM FUTURE FLOOR PLATE BMP-4 Shh Noggin DORSAL AORTA ROOF PLATE Products for Morphogen Research for Products Noggin Wnt-1 Wnt-3a Wnt-4 NT-3 Wnt-6 Wnt-7a EARLY SOMITE Myf5 NEURAL TUBE Pax3 Sim1 BMP-4 INTERMEDIATE MESODERM Shh ShhShh NogginNoggin BMP-4 DORSAL AORTA Ihh NOTOCHORD MORPHOGENS Morphogens are molecules that regulate cell fate during development. Formation of morphogen concentration gradients directs the biological responses of surrounding cells. Graded responses occur as a result of morphogens binding to specific cell surface receptors that subsequently activate intracellular signaling pathways and promote or repress gene expression at specific threshold concentrations. Activation or inactivation of these signaling pathways provides positional information that ultimately determines tissue organization and morphology. Research in model organisms has revealed that morphogens are involved in many aspects of development. For example, morphogens are required in Drosophila for patterning of the dorso-ventral and anterior-posterior axes, segment patterning, and positional signaling in the leg and wing imaginal discs. Proteins belonging to the Wingless/Wnt, Notch, Hedgehog, and TGF-b families have been identified as morphogens that direct a number of these processes. Research in higher organisms has demonstrated that homologues of these same signaling molecules regulate vertebrate axis formation, anterior/posterior polarity during limb development, mesoderm patterning, and numerous other processes that establish an organism’s basic body structure. R&D Systems offers a wide selection of proteins, antibodies, and ELISAs for morphogen-related developmental research. -
Rapid Changes in Morphogen Concentration Control Self-Organized
RESEARCH COMMUNICATION Rapid changes in morphogen concentration control self-organized patterning in human embryonic stem cells Idse Heemskerk1†, Kari Burt1, Matthew Miller1, Sapna Chhabra2, M Cecilia Guerra1, Lizhong Liu1, Aryeh Warmflash1,3* 1Department of Biosciences, Rice University, Houston, United States; 2Systems, Synthetic and Physical Biology Program, Rice University, Houston, United States; 3Department of Bioengineering, Rice University, Houston, United States Abstract During embryonic development, diffusible signaling molecules called morphogens are thought to determine cell fates in a concentration-dependent way. Yet, in mammalian embryos, concentrations change rapidly compared to the time for making cell fate decisions. Here, we use human embryonic stem cells (hESCs) to address how changing morphogen levels influence differentiation, focusing on how BMP4 and Nodal signaling govern the cell-fate decisions associated with gastrulation. We show that BMP4 response is concentration dependent, but that expression of many Nodal targets depends on rate of concentration change. Moreover, in a self- organized stem cell model for human gastrulation, expression of these genes follows rapid changes in endogenous Nodal signaling. Our study shows a striking contrast between the specific ways ligand dynamics are interpreted by two closely related signaling pathways, highlighting both the *For correspondence: subtlety and importance of morphogen dynamics for understanding mammalian embryogenesis [email protected] and designing optimized protocols for directed stem cell differentiation. Editorial note: This article has been through an editorial process in which the authors decide how † Present address: Department to respond to the issues raised during peer review. The Reviewing Editor’s assessment is that all of Cell and Developmental the issues have been addressed (see decision letter). -
Annominer Is a New Web-Tool to Integrate Epigenetics, Transcription
www.nature.com/scientificreports OPEN AnnoMiner is a new web‑tool to integrate epigenetics, transcription factor occupancy and transcriptomics data to predict transcriptional regulators Arno Meiler1,3, Fabio Marchiano2,3, Margaux Haering2, Manuela Weitkunat1, Frank Schnorrer1,2 & Bianca H. Habermann1,2* Gene expression regulation requires precise transcriptional programs, led by transcription factors in combination with epigenetic events. Recent advances in epigenomic and transcriptomic techniques provided insight into diferent gene regulation mechanisms. However, to date it remains challenging to understand how combinations of transcription factors together with epigenetic events control cell‑type specifc gene expression. We have developed the AnnoMiner web‑server, an innovative and fexible tool to annotate and integrate epigenetic, and transcription factor occupancy data. First, AnnoMiner annotates user‑provided peaks with gene features. Second, AnnoMiner can integrate genome binding data from two diferent transcriptional regulators together with gene features. Third, AnnoMiner ofers to explore the transcriptional deregulation of genes nearby, or within a specifed genomic region surrounding a user‑provided peak. AnnoMiner’s fourth function performs transcription factor or histone modifcation enrichment analysis for user‑provided gene lists by utilizing hundreds of public, high‑quality datasets from ENCODE for the model organisms human, mouse, Drosophila and C. elegans. Thus, AnnoMiner can predict transcriptional regulators for a studied -
Hox Gene Variation and Evolution
news and views annually degasses about 1 gigatonne (109 not nitrate exhaustion. on the microbial algae. The growth perfor- tonnes) of CO2 (ref. 3), equivalent to 20 per Yet the paradox persists. Virtually all phy- mance of the diatoms is all the more surpris- cent of current anthropogenic output. The toplankton species, including the picoplank- ing as nitrate reduction requires energy regression lines and intercepts of dissolved ton, are able to use nitrate; indeed, phyto- and the mediating enzyme contains iron. inorganic carbon, silicate and nitrate con- plankton other than diatoms routinely Indeed, why diatoms can be so much more centrations, measured in the upper 200 m of exhaust nitrate in the surface waters of the efficient than the other algae despite the the EUZ, indicate that silicate availability non-HNLC ocean. So why does this not hap- nitrate handicap needs to be explained. regulates both carbon and nitrate uptake pen in the EUZ and other low-silicate HNLC Balancing pelagic ecosystem budgets is and fate. The slope of the highly significant regions? Differences in grazing pressure still an art because we know so little about the 5 regression between nitrate and silicate is 1, have been proposed as an explanation . One abilities and predilections of the organisms8 which coincides with the known require- widely held view is that the small algae of the and their interactions with one another5. ment of these two elements by diatoms. The microbial loop are kept in check by heavy Whatever the outcome of studies on the lim- intercept represents the excess nitrate (about grazing pressure, whereas diatoms, because iting factors in the various HNLC regions 4 mmol m–3) that confers HNLC status on of their larger size (and possibly also the pro- and their subsystems, the status of diatoms as the EUZ. -
Evolutionary Developmental Biology 573
EVOC20 29/08/2003 11:15 AM Page 572 Evolutionary 20 Developmental Biology volutionary developmental biology, now often known Eas “evo-devo,” is the study of the relation between evolution and development. The relation between evolution and development has been the subject of research for many years, and the chapter begins by looking at some classic ideas. However, the subject has been transformed in recent years as the genes that control development have begun to be identified. This chapter looks at how changes in these developmental genes, such as changes in their spatial or temporal expression in the embryo, are associated with changes in adult morphology. The origin of a set of genes controlling development may have opened up new and more flexible ways in which evolution could occur: life may have become more “evolvable.” EVOC20 29/08/2003 11:15 AM Page 573 CHAPTER 20 / Evolutionary Developmental Biology 573 20.1 Changes in development, and the genes controlling development, underlie morphological evolution Morphological structures, such as heads, legs, and tails, are produced in each individual organism by development. The organism begins life as a single cell. The organism grows by cell division, and the various cell types (bone cells, skin cells, and so on) are produced by differentiation within dividing cell lines. When one species evolves into Morphological evolution is driven another, with a changed morphological form, the developmental process must have by developmental evolution changed too. If the descendant species has longer legs, it is because the developmental process that produces legs has been accelerated, or extended over time. -
Drosophila Pax6 Promotes Development of the Entire Eye-Antennal Disc, Thereby Ensuring Proper Adult Head Formation
PAPER Drosophila Pax6 promotes development of the entire COLLOQUIUM eye-antennal disc, thereby ensuring proper adult head formation Jinjin Zhua, Sneha Palliyila, Chen Ranb, and Justin P. Kumara,1 aDepartment of Biology, Indiana University, Bloomington, IN 47405; and bDepartment of Biology, Stanford University, Stanford, CA 94305 Edited by Ellen V. Rothenberg, California Institute of Technology, Pasadena, CA, and accepted by Editorial Board Member Neil H. Shubin February 17, 2017 (received for review July 26, 2016) Paired box 6 (Pax6) is considered to be the master control gene for molecular battle among GRNs allows for the subdivision of the eye development in all seeing animals studied so far. In vertebrates, eye-antennal disc to be maintained within a single continuous it is required not only for lens/retina formation but also for the cellular field (13–16). Of the GRNs that are known to operate development of the CNS, olfactory system, and pancreas. Although within the eye-antennal disc, the retinal determination (RD) Pax6 plays important roles in cell differentiation, proliferation, and network, which controls eye development, is the best studied (17). patterning during the development of these systems, the underlying At the core of the RD network lie the Paired box 6 (Pax6) genes mechanism remains poorly understood. In the fruit fly, Drosophila eyeless (ey)andtwin of eyeless (toy), the SIX family member sine melanogaster, Pax6 also functions in a range of tissues, including oculis (so), the transcriptional coactivator eyes absent (eya), and the the eye and brain. In this report, we describe the function of Pax6 in Ski/Sno family member dachshund (dac)(17). -
Reduced H3k27me3 Leads to Abnormal Hox Gene Expression In
Yu et al. Epigenetics & Chromatin (2019) 12:76 https://doi.org/10.1186/s13072-019-0318-1 Epigenetics & Chromatin RESEARCH Open Access Reduced H3K27me3 leads to abnormal Hox gene expression in neural tube defects Juan Yu1†, Lei Wang2†, Pei Pei2†, Xue Li4, Jianxin Wu3, Zhiyong Qiu2, Juan Zhang1, Ruifang Ao1, Shan Wang2*, Ting Zhang2* and Jun Xie1* Abstract Background: Neural tube defects (NTDs) are severe, common birth defects that result from failure of normal neural tube closure during early embryogenesis. Accumulating strong evidence indicates that genetic factors contribute to NTDs etiology, among them, HOX genes play a key role in neural tube closure. Although abnormal HOX gene expres- sion can lead to NTDs, the underlying pathological mechanisms have not fully been understood. Method: We detected that H3K27me3 and expression of the Hox genes in a retinoic acid (RA) induced mouse NTDs model on E8.5, E9.5 and E10.5 using RNA-sequencing and chromatin immunoprecipitation sequencing assays. Furthermore, we quantifed 10 Hox genes using NanoString nCounter in brain tissue of fetuses with 39 NTDs patients including anencephaly, spina bifda, hydrocephaly and encephalocele. Results: Here, our results showed diferential expression in 26 genes with a > 20-fold change in the level of expres- sion, including 10 upregulated Hox genes. RT-qPCR revealed that these 10 Hox genes were all upregulated in RA- induced mouse NTDs as well as RA-treated embryonic stem cells (ESCs). Using ChIP-seq assays, we demonstrate that a decrease in H3K27me3 level upregulates the expression of Hox cluster A–D in RA-induced mouse NTDs model on E10.5. -
Role of HOX Genes in Stem Cell Differentiation and Cancer
Thomas Jefferson University Jefferson Digital Commons Kimmel Cancer Center Papers, Presentations, and Grand Rounds Kimmel Cancer Center 7-22-2018 Role of HOX Genes in Stem Cell Differentiation and Cancer. Seema Bhatlekar Helen F. Graham Cancer Center and Research Institute; University of Delaware Jeremy Z Fields CATX Inc. Bruce M. Boman Thomas Jefferson University; Helen F. Graham Cancer Center and Research Institute; University of Delaware; CATX Inc. Follow this and additional works at: https://jdc.jefferson.edu/kimmelgrandrounds Part of the Oncology Commons Let us know how access to this document benefits ouy Recommended Citation Bhatlekar, Seema; Fields, Jeremy Z; and Boman, Bruce M., "Role of HOX Genes in Stem Cell Differentiation and Cancer." (2018). Kimmel Cancer Center Papers, Presentations, and Grand Rounds. Paper 62. https://jdc.jefferson.edu/kimmelgrandrounds/62 This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in Kimmel Cancer Center Papers, Presentations, and Grand Rounds by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: [email protected]. Hindawi Stem Cells International Volume 2018, Article ID 3569493, 15 pages https://doi.org/10.1155/2018/3569493 Review Article Role of HOX Genes in Stem Cell Differentiation and Cancer 1,2 3 1,2,3,4 Seema Bhatlekar , Jeremy Z.