DOCSLIB.ORG

The Role of Hoxa2 and Characterization of Its New Downstream Targets in Murine Palatogenesis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Role of Hoxa2 and Characterization of Its New Downstream Targets in Murine Palatogenesis The Role of Hoxa2 and Characterization of its New Downstream Targets in Murine Palatogenesis A Thesis Submitted to the College of Graduate Studies and Research in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in the College of Pharmacy and Nutrition University of Saskatchewan Saskatoon By Tara Marie Smith © Copyright Tara Marie Smith, September 2009, All right reserved. PERMISSION TO USE In presenting this thesis in partial fulfillment of the requirements for a Doctor of Philosophy degree from the University of Saskatchewan, I agree that the Libraries of this University may make it freely available for inspection. I further agree that permission for copying this thesis in any manner, in whole or in part, for scholarly purposes may be granted by Dr. Adil J. Nazarali, the professor who supervised my thesis work, or in their absence, by the Dean of the College of Pharmacy and Nutrition in which my thesis work was done. It is understood that any copying or publication, or use of this thesis or parts thereof for financial gain shall not be allowed without my written permission. It is also understood that due recognition shall be given to me and to the University of Saskatchewan in any scholarly use which may be made of any material in my thesis. Requests for permission to copy or to make use of material in this thesis in whole or in part should be addressed to: Dean of the College of Pharmacy and Nutrition University of Saskatchewan 110 Science Place Saskatoon, Saskatchewan S7N 5C9 i Abstract Hoxa2 null embryos display a high incidence of cleft secondary palate which has previously been described as secondary to altered tongue development. The experiments described in this thesis demonstrate that expression of Hoxa2 does occur within the developing palate, with the highest levels appearing in the early stages of palatogenesis (E12.5 and E13.5). Increased cell proliferation was observed throughout the palate in the absence of Hoxa2, without a detectable difference in apoptosis or the ability of the shelves to fuse. In addition, the palate shelves of the null embryos failed to elevate above the tongue, suggesting a mechanism by which the increased cell proliferation results in cleft palate. Numerous downstream targets of Hoxa2 were also identified in the palate (Msx1, Bmp4, Barx1, Ptx1, Six2, Lef1 and Tbx1). In all cases, Hoxa2 appears to act as a transcriptional repressor. Increases in palatal Msx1, Bmp4 and Barx1 expression have all been previously described to lead to increases in cell proliferation. Hoxa2, Ptx1, Lef1 and Tbx1 may be involved in a novel pathway that regulates proliferation in the palate. In addition, three novel gene targets were identified in the palate, Six2, Fgf8 and Htra3. Together these data show that there is a direct role for Hoxa2 in regulating palate development, apparently through regulating the expression of downstream genes involved in maintaining normal cell proliferation rates. ii Acknowledgments This thesis would not have been possible without the support of many individuals. I would like to thank Dr. Adil Nazarali for his guidance and support over the past five years, in both my professional and personal life. I would also like to thank my committee members, Dr. William Kulyk, Dr. Baljit Singh and Dr. Phyllis Paterson for their support and suggestions throughout this process. Also thanks to my external examiner Dr. Scott Lozanoff for taking time out of his busy schedule to review my research and act on my committee. I would like to thank the members of my lab especially LaRhonda Sobchishin. She provided constant encouragement and support and acted as a wealth of technical information. Thank you to my fellow graduate students especially Erin Prosser-Loose and Barbara McEwen with whom I have developed a special friendship due to the incredible ups and downs that grad school as put us through together. iii Dedication This is dedicated to my ever supportive family. To my mother, Elaine Smith, who taught me how to be a strong, confident woman that when she puts her mind to it can do anything. To my father, Curt Smith, who has been behind me everyday with love and encouragement. To my sister, Shari Smith, who constantly reminds me what is important in life. Finally to my husband, Scott Caswell, who has been there for me through all the ups and downs of the past couple of years, and whose confidence in me has never waivered. iv Table of Contents Permission to Use ...................................................................................................... i Abstract ..................................................................................................................... ii Acknowledgements ...................................................................................................iii Dedication ................................................................................................................ iv Table of Contents ...................................................................................................... v List of Figures ............................................................................................................ x List of Abbreviations .................................................................................................xii 1.0 Introduction ......................................................................................................... 1 2.0 Hypothesis and Objectives .................................................................................. 3 3.0 Literature Review ................................................................................................ 4 3.1 Overview of Craniofacial Development ...................................................... 4 3.2 Cranial Neural Crest Cell Migration ............................................................ 4 3.3 Facial Development .................................................................................. 10 3.3.1 Secondary Palate Development .................................................. 12 3.3.1.1 Cleft Palate .................................................................. 17 3.4 Molecular Signalling within the Palate ...................................................... 19 3.4.1 Gene Signalling that Regulates Proliferation in the Palate ......... 22 3.4.1.1 Msx1 Signalling Pathway .............................................. 22 3.4.1.2 Bone Morphogenic Protein Signalling Pathway ............ 26 3.4.1.3 Sonic Hedgehog Signalling Pathway ............................ 28 3.4.1.4 Sprouty2 Signalling Pathway ........................................ 30 v 3.4.1.5 Barx1 Signalling Pathway ............................................. 31 3.4.1.6 Tbx22 Signalling Pathway ............................................ 32 3.4.1.7 Fgf10 Signalling Pathway ............................................. 34 3.4.1.8 Fgf Receptors ............................................................... 36 3.4.1.9 Shox2 Signalling Pathway ............................................ 36 3.4.2 Regulation of Palatal Shelf Fusion............................................. 37 3.4.2.1 Transforming Growth Factors Signalling Pathway ......... 38 3.4.2.2 Epidermal Growth Factor Signalling Pathway ................ 40 3.4.2.3 Meox2 Signalling Pathway ............................................. 42 3.4.2.4 Fgf10 Signalling Pathway .............................................. 43 1.4.3 Cell Migration............................................................................. 43 3.5 Homeobox genes .......................................................................................... 46 3.5.1 Hoxa2 ......................................................................................... 53 3.5.1.1 Regulation of Hoxa2 Expression .................................. 54 3.5.1.2 Hoxa2 Mutant Phenotypes ........................................... 56 3.5.1.3 Hoxa2‟s Involvement in Palate Development ............... 58 3.5.1.4 Putative Downstream Targets of Hoxa2 in the Palate .. 59 3.5.1.4.1 Msx1 .............................................................. 59 3.5.1.4.2 Htra3 .............................................................. 60 3.5.1.4.3 Six2 ................................................................ 61 3.5.1.4.4 Ptx1 ............................................................... 62 3.6 Summary ....................................................................................... 63 vi 4.0 Materials and Methods ...................................................................................... 65 4.1 Hoxa2 Transgenic Mice ................................................................. 65 4.1.1 PCR Analysis of Genotype .......................................... 65 4.2 Immunohistochemical Analysis.................................................... 66 4.2.1 Fgf8, Six2 and Activated Caspase 3 ............................. 66 4.2.2 Htra3 and Hoxa2 .......................................................... 69 4.3 Cell Proliferation Assay ................................................................. 70 4.4 TUNEL Assay ................................................................................ 71 4.5 Whole Palate Organ Cultures ........................................................ 72 4.6 Western Blot Analysis .................................................................... 76 4.7 RNA Isolation and Reverse Transcription ...................................... 78 4.8 Quantitative Real Time RT-PCR...................................................
Load more

Recommended publications
  • During Early Embryogenesis HEIDRUN ELLINGER-ZIEGELBAUER,' ABDELMADJID K
    MOLECULAR AND CELLULAR BIOLOGY, Apr. 1994, p. 2786-2797 Vol. 14, No. 4 0270-7306/94/$04.00+0 Copyright © 1994, American Society for Microbiology FTZ-F1-Related Orphan Receptors in Xenopus laevis: Transcriptional Regulators Differentially Expressed during Early Embryogenesis HEIDRUN ELLINGER-ZIEGELBAUER,' ABDELMADJID K. HIHI,2 VINCENT LAUDET,3 HANSJORG KELLER,2 WALTER WAHLI,2 AND CHRISTINE DREYER'* Max-Planck-Institut far Entwicklungsbiologie, D-72011 Tubingen, Federal Republic of Germany'; Institut de Biologie Animale, Universite de Lausanne, CH-1015 Lausanne, Switzerland ; and Unite d'Oncologie Moleculaire, Institut Pasteur, 59019 Lille Cedex, France3 Received 27 October 1993/Returned for modification 1 December 1993/Accepted 10 January 1994 Orphan receptors of the FTZ-F1-related group of nuclear receptors (xFFlr) were identified in Xenopus laevis by isolation of cDNAs from a neurula stage library. Two cDNAs were found, which encode full-length, highly related receptor proteins, xFFlrA and B, whose closest relative known so far is the murine LRH-1 orphan receptor. xFFIrA protein expressed by a recombinant vaccinia virus system specifically binds to f1Z-F1 response elements (FRE; PyCAAGGPyCPu). In cotransfection studies, xFF1rA constitutively activates transcription, in a manner dependent on the number of FREs. The amounts of at least four mRNAs encoding full-length receptors greatly increase between gastrula and early tailbud stages and decrease at later stages. At early tailbud stages, xFTZ-F1-related antigens are found in all nuclei of the embryo. The nuclear hormone receptor superfamily includes recep- yet another class of receptors (type III). They most probably tors for steroid and thyroid hormones, vitamin D and retinoic bind as monomers to extended, unrepeated half-site motifs.
    [Show full text]
  • Pharmacogene Regulatory Elements: from Discovery to Applications
    Smith et al. Genome Medicine 2012, 4:45 http://genomemedicine.com/content/4/5/45 REVIEW Pharmacogene regulatory elements: from discovery to applications Robin P Smith1,2†, Ernest T Lam2,3†, Svetlana Markova1, Sook Wah Yee1* and Nadav Ahituv1,2* Pharmacogenomics and gene regulatory elements: Abstract an emerging picture Regulatory elements play an important role in the Most pharmacogenomics studies to date have focused on variability of individual responses to drug treatment. coding variants of pharmacologically important proteins. This has been established through studies on three However, well-supported examples of variants in regu la- classes of elements that regulate RNA and protein tory elements of genes involved in drug response, such as abundance: promoters, enhancers and microRNAs. drug metabolizing enzymes and transporters (see review Each of these elements, and genetic variants within by Georgitsi et al. [1]), show that variants in noncoding them, are being characterized at an exponential pace regulatory sequences are also likely to be important by next-generation sequencing (NGS) technologies. In (Table 1). Th ree classes of regulatory elements have been this review, we outline examples of how each class of studied in this context: promoters, enhancers and element aff ects drug response via regulation of drug microRNAs (miRNAs). Each of these has a direct impact targets, transporters and enzymes. We also discuss on the abundance of messenger RNA (mRNA) (in the case the impact of NGS technologies such as chromatin of promoters and enhancers) and protein (in the case of immunoprecipitation sequencing (ChIP-Seq) and RNA miRNAs). Genetic variation within each of these elements sequencing (RNA-Seq), and the ramifi cations of new has been linked to human disease as well as interindividual techniques such as high-throughput chromosome diff erences in drug response.
    [Show full text]
  • 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).
    [Show full text]
  • An Extension of the Pax6 Allelic Series and the Identification Of
    Copyright 2001 by the Genetics Society of America Molecular Characterization of Pax62Neu Through Pax610Neu: An Extension of the Pax6 Allelic Series and the Identification of Two Possible Hypomorph Alleles in the Mouse Mus musculus Jack Favor,* Heiko Peters,*,1 Thomas Hermann,† Wolfgang Schmahl,‡ Bimal Chatterjee,* Angelika Neuha¨user-Klaus* and Rodica Sandulache* *Institute of Mammalian Genetics, GSF-Research Center for Environment and Health, Neuherberg D-85764, Germany, †Memorial Sloan-Kettering Cancer Center, New York, New York 10021 and ‡Lehrstuhl fu¨r Allgemeine Pathologie und Neuropathologie, Tiera¨rztliche Fakulta¨t, Ludwig-Maximilians-Universita¨t, Mu¨nchen D-80539, Germany Manuscript received April 27, 2001 Accepted for publication September 28, 2001 ABSTRACT Phenotype-based mutagenesis experiments will increase the mouse mutant resource, generating muta- tions at previously unmarked loci as well as extending the allelic series at known loci. Mapping, molecular characterization, and phenotypic analysis of nine independent Pax6 mutations of the mouse recovered in mutagenesis experiments is presented. Seven mutations result in premature termination of translation and all express phenotypes characteristic of null alleles, suggesting that Pax6 function requires all domains to be intact. Of major interest is the identification of two possible hypomorph mutations: Heterozygotes express less severe phenotypes and homozygotes develop rudimentary eyes and nasal processes and survive up to 36 hr after birth. Pax6 4Neu results in an amino acid substitution within the third helix of the homeodomain. Three-dimensional modeling indicates that the amino acid substitution interrupts the homeodomain recognition ␣-helix, which is critical for DNA binding. Whereas cooperative dimer binding of the mutant homeodomain to a paired-class DNA target sequence was eliminated, weak monomer binding was observed.
    [Show full text]
  • DLX Genes: Roles in Development and Cancer
    cancers Review DLX Genes: Roles in Development and Cancer Yinfei Tan 1,* and Joseph R. Testa 1,2,* 1 Genomics Facility, Fox Chase Cancer Center, Philadelphia, PA 19111, USA 2 Cancer Signaling and Epigenetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA * Correspondence: [email protected] (Y.T.); [email protected] (J.R.T.) Simple Summary: DLX homeobox family genes encode transcription factors that have indispensable roles in embryonic and postnatal development. These genes are critically linked to the morphogene- sis of craniofacial structures, branchial arches, forebrain, and sensory organs. DLX genes are also involved in postnatal homeostasis, particularly hematopoiesis and, when dysregulated, oncogen- esis. DLX1/2, DLX3/4, and DLX5/6 exist as bigenes on different chromosomes, sharing intergenic enhancers between gene pairs, which allows orchestrated spatiotemporal expression. Genomic alterations of human DLX gene enhancers or coding sequences result in congenital disorders such as split-hand/foot malformation. Aberrant postnatal expression of DLX genes is associated with hematological malignancies, including leukemias and lymphomas. In several mouse models of T-cell lymphoma, Dlx5 has been shown to act as an oncogene by cooperating with activated Akt, Notch1/3, and/or Wnt to drive tumor formation. In humans, DLX5 is aberrantly expressed in lung and ovarian carcinomas and holds promise as a therapeutic target. Abstract: Homeobox genes control body patterning and cell-fate decisions during development. The homeobox genes consist of many families, only some of which have been investigated regarding a possible role in tumorigenesis. Dysregulation of HOX family genes have been widely implicated in cancer etiology.
    [Show full text]
  • Phylogenetic Analysis of T-Box Genes Demonstrates the Importance of Amphioxus for Understanding Evolution of the Vertebrate Genome
    Copyright 2000 by the Genetics Society of America Phylogenetic Analysis of T-Box Genes Demonstrates the Importance of Amphioxus for Understanding Evolution of the Vertebrate Genome Ilya Ruvinsky,1 Lee M. Silver and Jeremy J. Gibson-Brown Lewis Thomas Laboratory, Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544 Manuscript received September 20, 1999 Accepted for publication June 29, 2000 ABSTRACT The duplication of preexisting genes has played a major role in evolution. To understand the evolution of genetic complexity it is important to reconstruct the phylogenetic history of the genome. A widely held view suggests that the vertebrate genome evolved via two successive rounds of whole-genome duplication. To test this model we have isolated seven new T-box genes from the primitive chordate amphioxus. We ®nd that each amphioxus gene generally corresponds to two or three vertebrate counterparts. A phyloge- netic analysis of these genes supports the idea that a single whole-genome duplication took place early in vertebrate evolution, but cannot exclude the possibility that a second duplication later took place. The origin of additional paralogs evident in this and other gene families could be the result of subsequent, smaller-scale chromosomal duplications. Our ®ndings highlight the importance of amphioxus as a key organism for understanding evolution of the vertebrate genome. OMPARISONS of the genomes of a wide variety nomenon known as the ªC-value paradoxº (Li 1997). C of organisms have revealed that the evolution of However, an even more precise approach is to compare genome complexity has not proceeded by nucleotide the number of genes within different gene families pres- substitution alone, but rather has relied on extensive ent in both vertebrate and invertebrate genomes.
    [Show full text]
  • The Homeodomain of Eyeless Regulates Cell Growth and Antagonizes the Paired Domain- Dependent Retinal Differentiation Function
    Protein Cell 2015, 6(1):68–78 DOI 10.1007/s13238-014-0101-9 Protein & Cell RESEARCH ARTICLE The homeodomain of Eyeless regulates cell growth and antagonizes the paired domain- dependent retinal differentiation function Miho Tanaka-Matakatsu, John Miller, Wei Du& Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA & Correspondence: [email protected] (W. Du) Received July 1, 2014 Accepted August 12, 2014 Cell & ABSTRACT KEYWORDS Pax6, eyeless, paired domain, homeodomain, cell growth, retinal differentiation Pax6 and its Drosophila homolog Eyeless (Ey) play essential roles during eye development. Ey/Pax6 con- tains two distinct DNA binding domains, a Paired INTRODUCTION Protein domain (PD) and a Homeodomain (HD). While Ey/Pax6 PD is required for the expression of key regulators of Pax6 is an evolutionary conserved transcription factor and is retinal development, relatively little is known about the indispensable for eye development. Mutations in Pax6 HD-dependent Ey function. In this study, we used the genes cause eye developmental defects in a wide range of UAS/GAL4 system to determine the functions of differ- species. In Drosophila and mouse, null mutations of Pax6 ent Ey domains on cell growth and on retinal develop- orthologs eyeless (ey) and small eye (Sey) cause severe ment. We showed that Ey can promote cell growth, defects in the eye (Hill et al., 1991; Quiring et al., 1994). In which requires the HD but not the PD. In contrast, the humans, heterozygous Pax6 gene mutations are associated ability of Ey to activate Ato expression and induce with eye disorders such as aniridia, Peters anomaly, and ectopic eye formation requires the PD but not the HD.
    [Show full text]
  • Antennapedia Is Involved in the Development of Thoracic Legs and Segmentation in the Silkworm, Bombyx Mori
    Heredity (2013) 111, 182–188 & 2013 Macmillan Publishers Limited All rights reserved 0018-067X/13 www.nature.com/hdy ORIGINAL ARTICLE Antennapedia is involved in the development of thoracic legs and segmentation in the silkworm, Bombyx mori P Chen1,3, XL Tong1,3,DDLi1,MYFu1,SZHe1,HHu1, ZH Xiang1,CLu1 and FY Dai1,2 Homeotic genes, which are associated closely with body patterning of various species, specify segment identity. The Wedge eye-spot (Wes) is a new homeotic mutant located on the sixth linkage group. Homozygous Wes/Wes embryos are lethal and display a pair of antenna-like appendages under the mouthparts as well as fused thoracic segments. These mutants also exhibit a narrower eye-spot at the larval stage compared with the wild type. By positional cloning, we identified the candidate gene of the Wes locus, Bombyx mori Antennapedia (BmAntp). Two BmAntp transcripts were identified in the homozygote of the Wes mutant, including a normal form and an abnormal form with a 1570-bp insertion. Our data showed that the insertion element was a long interspersed nuclear element (LINE)-like transposon that destroyed the original open reading frame of BmAntp. Quantitative RT-PCR analysis showed that the expression levels of normal BmAntp transcripts were increased markedly in the Wes heterozygous larvae compared with the wild type. Furthermore, we performed RNAi of BmAntp and observed fused thoracic segments and defective thoracic legs in the developing embryos. Our results indicated that BmAntp is responsible for the Wes mutant and has an important role in determining the proper development of the thoracic segments.
    [Show full text]
  • A Homeotic Gene of the Antennapedia Complex
    Development 113, 257-271 (1991) 257 Printed in Great Britain © The Company of Biologists Limited 1991 Rescue and regulation of proboscipedia: a homeotic gene of the Antennapedia Complex FILIPPO M. RANDAZZO, DAVID L. CRIBBS* and THOMAS C. KAUFMAN Howard Hughes Medical Institute, Institute for Cellular and Molecular Biology, and Programs in Genetics and Cellular, Molecular, and Developmental Biology, Department of Biology, Indiana University, Bloomington, Indiana, U.S.A. * Present address: Centre de Recherche de Biochimie et Genetique Cellulaires, 118, route de Narbonne 31062 Toulouse Cedex, France Summary The extraordinary positional conservation of the hom- minigene expresses pb protein in only a subset of pb's eotic genes within the Antennapedia and the Bithorax normal domains of expression. Therefore, the biological Complexes (ANT-C and BX-C) in Drosophila melanogas- significance of the excluded expression pattern elements ter and the murine Hox and human HOX clusters of remains unclear except to note they appear unnecessary genes can be interpreted as a reflection of functional for specifying normal labial identity. Additionally, by necessity. The homeotic gene proboscipedia (pb) resides using reporter gene constructs inserted into the Dros- within the ANT-C, and its sequence is related to that of ophila genome and by comparing /^-associated genomic Hox-1.5. We show that two independent pb minigene sequences from two divergent species, we have located P-element insertion lines completely rescue the labial m-acting regulatory elements required for pb expression palp-to-first leg homeotic transformation caused by pb in embryos and larvae. null mutations; thus, a homeotic gene of the ANT-C can properly carry out its homeotic function outside of the Key words: proboscipedia, homeotic gene, Antennapedia complex.
    [Show full text]
  • Hox Gene Collinearity May Be Related to Noether Theory on Symmetry and Its Linked Conserved Quantity
    Article Hox Gene Collinearity May Be Related to Noether Theory on Symmetry and Its Linked Conserved Quantity Spyros Papageorgiou Insitute of Biosciences and Applications, National Center for Scientific Research ‘Demokritos’, 15310 Athens, Greece; [email protected] Received: 5 March 2020; Accepted: 17 April 2020; Published: 24 April 2020 Abstract: Hox Gene Collinearity (HGC) is a fundamental property that controls the development of many animal species, including vertebrates. In the Hox gene clusters, the genes are located in a sequential order Hox1, Hox2, Hox3, etc., along the 3’ to 5’ direction of the cluster in the chromosome. During Hox cluster activation, the Hox genes are expressed sequentially in the ontogenetic units D1, D2, D3, etc., along the anterior–posterior axis (A-P) of the early embryo. This collinearity, first observed by E.B. Lewis, is surprising because the spatial collinearity of these structures (Hox clusters and embryos) correlates entities that differ by about four orders of magnitude. Biomolecular mechanisms alone cannot explain such correlations. Long-range physical interactions, such as diffusion or electric attractions, should be involved. A biophysical model (BM) was formulated, which, in alignment with the biomolecular processes, successfully describes the existing vertebrate genetic engineering data. One hundred years ago, Emmy Noether made a fundamental discovery in mathematics and physics. She proved, rigorously, that a physical system obeying a symmetry law (e.g., rotations or self-similarity) is followed by a conserved physical quantity. It is argued here that HGC obeys a ‘primitive’ self-similarity symmetry. In this case, the associated primitive conserved quantity is the irreversibly increasing ‘ratchet’-like Hoxgene ordering where some genes may be missing.
    [Show full text]
  • Drosophila Information Service
    Drosophila Information Service Number 103 December 2020 Prepared at the Department of Biology University of Oklahoma Norman, OK 73019 U.S.A. ii Dros. Inf. Serv. 103 (2020) Preface Drosophila Information Service (often called “DIS” by those in the field) was first printed in March, 1934. For those first issues, material contributed by Drosophila workers was arranged by C.B. Bridges and M. Demerec. As noted in its preface, which is reprinted in Dros. Inf. Serv. 75 (1994), Drosophila Information Service was undertaken because, “An appreciable share of credit for the fine accomplishments in Drosophila genetics is due to the broadmindedness of the original Drosophila workers who established the policy of a free exchange of material and information among all actively interested in Drosophila research. This policy has proved to be a great stimulus for the use of Drosophila material in genetic research and is directly responsible for many important contributions.” Since that first issue, DIS has continued to promote open communication. The production of this volume of DIS could not have been completed without the generous efforts of many people. Except for the special issues that contained mutant and stock information now provided in detail by FlyBase and similar material in the annual volumes, all issues are now freely-accessible from our web site: www.ou.edu/journals/dis. For early issues that only exist as aging typed or mimeographed copies, some notes and announcements have not yet been fully brought on line, but key information in those issues is available from FlyBase. We intend to fill in those gaps for historical purposes in the future.
    [Show full text]
  • The YPWM Motif Links Antennapedia to the Basal Transcriptional Machinery
    RESEARCH ARTICLE 1669 Development 135, 1669-1679 (2008) doi:10.1242/dev.018028 The YPWM motif links Antennapedia to the basal transcriptional machinery Frédéric Prince1, Tomonori Katsuyama2, Yoshiteru Oshima2, Serge Plaza3, Diana Resendez-Perez4, Meera Berry5, Shoichiro Kurata2 and Walter J. Gehring1,* HOX genes specify segment identity along the anteroposterior axis of the embryo. They code for transcription factors harbouring the highly conserved homeodomain and a YPWM motif, situated amino terminally to it. Despite their highly diverse functions in vivo, HOX proteins display similar biochemical properties in vitro, raising the question of how this specificity is achieved. In our study, we investigated the importance of the Antennapedia (Antp) YPWM motif for homeotic transformations in adult Drosophila. By ectopic overexpression, the head structures of the fly can be transformed into structures of the second thoracic segment, such as antenna into second leg, head capsule into thorax (notum) and eye into wing. We found that the YPWM motif is absolutely required for the eye-to-wing transformation. Using the yeast two-hybrid system, we were able to identify a novel ANTP-interacting protein, Bric-à-brac interacting protein 2 (BIP2), that specifically interacts with the YPWM motif of ANTP in vitro, as well as in vivo, transforming eye to wing tissue. BIP2 is a TATA-binding protein associated factor (also known as dTAFII3) that links ANTP to the basal transcriptional machinery. KEY WORDS: ANTP, HOX, bip2, dTAF3, Drosophila, Eye-to-wing transformation, Homeotic transformation INTRODUCTION in conferring specificity (Lin and McGinnis, 1992; Chan and Mann, Homeotic genes (HOX) are selector genes that generate 1993; Zeng et al., 1993; Chauvet et al., 2000; Gebelein et al., 2002; morphological diversity along the anteroposterior body axis during Merabet et al., 2003).
    [Show full text]