DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 9,506.065 B2 Croce Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 9,506.065 B2 Croce Et Al USOO9506065B2 (12) United States Patent (10) Patent No.: US 9,506.065 B2 Croce et al. (45) Date of Patent: Nov. 29, 2016 (54) DIAGNOSIS AND TREATMENT OF (2013.01); C12N 23 10/31 (2013.01); C12N CANCERS WITH MICRORNA LOCATED IN 23.10/32 (2013.01); C12N 23.10/33 (2013.01); OR NEAR CANCER-ASSOCATED CI2O 2600/106 (2013.01); C12O 2600/158 CHROMOSOMAL FEATURES (2013.01); C12O 2600/178 (2013.01) (58) Field of Classification Search (71) Applicant: Thomas Jefferson University, CPC ............................. A61K 48/00; C12N 15/113 Philadelphia, PA (US) See application file for complete search history. (72) Inventors: Carlo M. Croce, Columbus, OH (US); Chang-Gong Liu, Pearland, TX (US); (56) References Cited George A. Calin, Pearland, TX (US); Cinzia Sevignani, Philadelphia, PA U.S. PATENT DOCUMENTS (US) 7,723,030 B2 5, 2010 Croce et al. 8,778,676 B2 7/2014 Croce et al. (73) Assignee: Thomas Jefferson University, 2008/0261908 A1 10/2008 Croce et al. Philadelphia, PA (US) 2008/0306006 A1 12/2008 Croce et al. 2008/0306017 A1 12/2008 Croce et al. (*) Notice: Subject to any disclaimer, the term of this 2008/0306018 A1 12/2008 Croce et al. patent is extended or adjusted under 35 2010/0203544 A1 8, 2010 Croce et al. U.S.C. 154(b) by 2 days. (Continued) (21) Appl. No.: 14/846,193 FOREIGN PATENT DOCUMENTS (22) Filed: Sep. 4, 2015 WO WO O3,O29459 4/2003 WO WO O3,O29459 A2 4/2003 (65) Prior Publication Data (Continued) US 2015/0368647 A1 Dec. 24, 2015 OTHER PUBLICATIONS Related U.S. Application Data Amendment After Allowance dated Feb. 2, 2010, U.S. Appl. No. 11/194,055. “Diagnosis and Treatment of Cancers With MicroRNA (60) Division of application No. 14/281,756, filed on May Located in or Near Cancer-Associated Chromosomal Features.” 19, 2014, now Pat. No. 9,150,859, which is a continuation of application No. 13/972,759, filed on (Continued) Aug. 21, 2013, now Pat. No. 8,778,676, which is a division of application No. 12/767,279, filed on Apr. 26, 2010, now abandoned, which is a continuation of Primary Examiner — Amy Bowman application No. 11/194,055, filed on Jul. 29, 2005, (74) Attorney, Agent, or Firm — Hamilton, Brook, Smith now Pat. No. 7,723,030, which is a & Reynolds, P.C. continuation-in-part of application No. PCT/US2005/004865, filed on Feb. 9, 2005. (57) ABSTRACT (60) Provisional application No. 60/543,119, filed on Feb. 9, 2004, provisional application No. 60/542,929, filed MicroRNA genes are highly associated with chromosomal on Feb. 9, 2004, provisional application No. features involved in the etiology of different cancers. The 60/542,963, filed on Feb. 9, 2004, provisional perturbations in the genomic structure or chromosomal application No. 60/542,940, filed on Feb. 9, 2004, architecture of a cell caused by these cancer-associated provisional application No. 60/580,959, filed on Jun. chromosomal features can affect the expression of the miR 18, 2004, provisional application No. 60/580,797, gene(s) located in close proximity to that chromosomal filed on Jun. 18, 2004. feature. Evaluation of miR gene expression can therefore be used to indicate the presence of a cancer-causing chromo (51) Int. Cl. Somal lesion in a Subject. As the change in miR gene C7H 2L/02 (2006.01) expression level caused by a cancer-associated chromo C7H 2L/04 (2006.01) Somal feature may also contribute to cancerigenesis, a given A6 IK 4.8/00 (2006.01) cancer can be treated by restoring the level of miR gene CI2N IS/IT3 (2010.01) expression to normal. microRNA expression profiling can be CI2O I/68 (2006.01) used to diagnose cancer and predict whether a particular A6 IK3I/7088 (2006.01) cancer is associated with an adverse prognosis. The identi A6 IK3I/73 (2006.01) fication of specific mutations associated with genomic A6 IK 45/06 (2006.01) regions that harbor miR genes in CLL patients provides a (52) U.S. Cl. means for diagnosing CLL and possibly other cancers. CPC ....... CI2N 15/1135 (2013.01); A61 K3I/7088 (2013.01); A61 K3I/713 (2013.01); A61 K 45/06 (2013.01); C12N 15/113 (2013.01); 15 Claims, 9 Drawing Sheets CI2O I/6886 (2013.01); C12N 23 10/11 (6 of 9 Drawing Sheet(s) Filed in Color) US 9,506.065 B2 Page 2 (56) References Cited Bartel, D. P. “MicroRNAs. Genomics, Biogenesis, Mechanism, and Function.” Cell, 116(2):281-297 (Jan. 2004). U.S. PATENT DOCUMENTS Birren, B., et al., Homo sapiens chromosome 17, clone hRPC. 1073 F 15, complete sequence, GenBank Accession No. 2011/OO525O2 A1 3/2011 Croce et al. AC004686.1 online), Oct. 1998 retrieved on Apr. 23, 2014). 2014/0256040 A1 9, 2014 Croce et al. Retrieved from the Internet URL: www.ncbi.nlm.nih.gov/nuccore? ACOO46861 FOREIGN PATENT DOCUMENTS Calin, G. A., et al., “A MicroRNA Signature Associated with WO WO 2004/043387 A2 5, 2004 Prognosis and Progression in Chronic Lymphocytic Leukemia,” N. WO WO 2005/O13901 A2 2, 2005 Engl. J. Med., 353 (17): 1793-1801 (Oct. 2005). Calin, G. A., et al., “Frequent Deletions and Down-Regulation of Micro-RNA Genes miR15 and miR16 at 13c, 14 in Chronic OTHER PUBLICATIONS Lymphocytic Leukemia,” Proc. Natl. Acad. Sci. USA, 99 (24): 15524-15529 (Oct. 2002). Notice of Non-Compliant Amendment (37 CFR 1.121) dated Oct. 7, Calin, G. A. et al., “Human MicroRNA Genes are Frequently 2009, U.S. Appl. No. 11/194,055, "Diagnosis and Treatment of Located at Fragile Sites and Genomic Regions Involved in Can Cancers With MicroRNA Located in or Near Cancer-Associated cers.” Proc. Natl. Acad. Sci. USA, 101 (9):2999-3004 (Mar. 2004). Chromosomal Features.” Calin, G. A., et al., “MicroRNA Profiling Reveals Distinct Signa Office Action dated Jun. 13, 2012, U.S. Appl. No. 12/751,463, tures in B Cell Chronic Lymphocytic Leukemias.” Proc. Natl. Acad. “Diagnosis and Treatment Of Cancers With MicroRNA Located in Sci. USA, 101 (32): 11755-11760 (Jun. 2004). or Near Cancer Associated Chromosomal Features.” Chen et al., “Micro-RNA-21 regulates the sensitivity to cisplatin in Office Action dated Mar. 18, 2009, U.S. Appl. No. 11/194,055, human neuroblastoma cells,” J. Pediatr. Surg. 47(10): 1797-1805 “Diagnosis and Treatment of Cancers With MicroRNA Located in (2012). or Near Cancer-Associated Chromosomal Features.” Cheung, et al., “Natural variation in human gene expression Reply dated Jul. 16, 2009, U.S. Appl. No. 11/194,055. “Diagnosis assessed in lymphoblastoid cells,” Nature Genetics, 2003, vol. 33. and Treatment Of Cancers With MicroRNA Located in or Near p. 422. Cancer-Associated Chromosomal Features.” Cobb, et al., “Sepsis gene expression profiling: Murine splenic Reply to Restriction Requirement dated Dec. 16, 2008, U.S. Appl. compared with hepatic responses determined by using complemen No. 11/194,055, "Diagnosis and Treatment of Cancers With MicroRNA Located in or Near Cancer-Associated Chromosomal tary DNA microarrays.” Crit Care Med. 2002, vol. 30, p. 2711. Features. Communication Pursuant to Article 94(3) EPC dated Dec. 13, 2007. Reply to Restriction Requirement dated Jul. 7, 2008, U.S. Appl. No. Application No. EP 05 723130.0, "Diagnosis and Treatment of 11/194,055, "Diagnosis and Treatment of Cancers With MicroRNA Cancers With MicroRna Located in or Near Cancer-Associated Located in or Near Cancer-Associated Chromosomal Features.” Chromosomal Features.” Reply to Restriction Requirement dated Mar. 5, 2008, U.S. Appl. Esquela-Kerscher, A., et al. “Oncomirs—microRNAs with a role in No. 11/194,055, "Diagnosis and Treatment of Cancers With cancer,” Nat Rev Cancer, 6(4): 259-269 (Apr. 2006). MicroRNA Located in or Near Cancer-Associated Chromosomal European Search Report and Written Opinion dated Apr. 12, 2012, Features. Application No. EP 10 17 9994, "Diagnosis and Treatment of Restriction Requirement dated Feb. 13, 2012, U.S. Appl. No. Cancers With MicroRna Located in or Near Cancer-Associated 12,751,463, “Diagnosis and Treatment of Cancers With MicroRNA Chromosomal Features.” Located in or Near Cancer Associated Chromosomal Features.” Examination Report dated Apr. 12, 2013, Application No. EP 1017 Restriction Requirement dated May 23, 2008, U.S. Appl. No. 9994, "Diagnosis and Treatment of Cancers With MicroRna 11/194,055. “Diagnosis and Treatment of Cancers With MicroRNA Located in or Near Cancer-Associated Chromosomal Features.” Located in or Near Cancer-Associated Chromosomal Features.” Fabbri et al., “MicroRNAs bind to Toll-like receptors to induce Restriction Requirement dated Sep. 20, 2007 U.S. Appl. No. prometastatic inflammatory response.” PNAS 109(31): E2110 11/194,055. “Diagnosis and Treatment of Cancers With MicroRNA E2116 (2012). Located in or Near Cancer-Associated Chromosomal Features.” Fabbri, M. and R. Garzon, “Implications of MicroRNAs in Normal Supplemental Amendment dated Oct. 15, 2009.U.S. Appl. No. Hematopoiesis and Human Leukemia,” Clinical Leukemia, 2.96 11/194,055. “Diagnosis and Treatment of Cancers With MicroRNA 101 (May 2008). Located in or Near Cancer-Associated Chromosomal Features.” Fei, J., et al., “Inhibitory effects of anti-miRNA oligonucleotides Petition Decision for U.S. Appl. No. 14/281,756, "Diagnosis and (AMOs) on A549 cell growth.” J. Drug Target 16(9): 688-693 Treatment of Cancers With MicroRNA Located in or Near Cancer (2008). Associated Chromosomal Features', date of mailing Sep. 2, 2015. Ferracin, M., et al., “MicroRNAs involvement infludarabine refrac Notice of Allowance for U.S. Appl. No. 14/281,756, "Diagnosis and tory chronic lymphocytic leukemia,” Molecular Cancer, 9:123, 14 Treatment of Cancers With MicroRNA Located in or Near Cancer pages (2010), doi:10.1186/1476-4598-9-123.
Load more

Recommended publications
  • Differential Regulation of Parahox Genes by Retinoic Acid in the Invertebrate Chordate Amphioxus (Branchiostoma floridae)
    Developmental Biology 327 (2009) 252–262 Contents lists available at ScienceDirect Developmental Biology journal homepage: www.elsevier.com/developmentalbiology Evolution of Developmental Control Mechanisms Differential regulation of ParaHox genes by retinoic acid in the invertebrate chordate amphioxus (Branchiostoma floridae) Peter W. Osborne a,1, Gérard Benoit b, Vincent Laudet b, Michael Schubert b,2, David E.K. Ferrier a,⁎,1,2 a Zoology Department, Oxford University, South Parks Road, Oxford, OX1 3PS, UK b Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, CNRS, INRA, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France article info abstract Article history: The ParaHox cluster is the evolutionary sister to the Hox cluster. Like the Hox cluster, the ParaHox cluster Received for publication 2 October 2008 displays spatial and temporal regulation of the component genes along the anterior/posterior axis in a Revised 19 November 2008 manner that correlates with the gene positions within the cluster (a feature called collinearity). The ParaHox Accepted 19 November 2008 cluster is however a simpler system to study because it is composed of only three genes. We provide a Available online 7 December 2008 detailed analysis of the amphioxus ParaHox cluster and, for the first time in a single species, examine the regulation of the cluster in response to a single developmental signalling molecule, retinoic acid (RA). Keywords: Amphioxus Embryos treated with either RA or RA antagonist display altered ParaHox gene expression: AmphiGsx Retinoic acid expression shifts in the neural tube, and the endodermal boundary between AmphiXlox and AmphiCdx shifts Gsx its anterior/posterior position.
    [Show full text]
  • Divergent Genes in Gerbils: Prevalence, Relation to GC-Biased Substitution, and Phenotypic Relevance Yichen Dai, Rodrigo Pracana and Peter W
    Dai et al. BMC Evolutionary Biology (2020) 20:134 https://doi.org/10.1186/s12862-020-01696-3 RESEARCH ARTICLE Open Access Divergent genes in gerbils: prevalence, relation to GC-biased substitution, and phenotypic relevance Yichen Dai, Rodrigo Pracana and Peter W. H. Holland* Abstract Background: Two gerbil species, sand rat (Psammomys obesus) and Mongolian jird (Meriones unguiculatus), can become obese and show signs of metabolic dysregulation when maintained on standard laboratory diets. The genetic basis of this phenotype is unknown. Recently, genome sequencing has uncovered very unusual regions of high guanine and cytosine (GC) content scattered across the sand rat genome, most likely generated by extreme and localized biased gene conversion. A key pancreatic transcription factor PDX1 is encoded by a gene in the most extreme GC-rich region, is remarkably divergent and exhibits altered biochemical properties. Here, we ask if gerbils have proteins in addition to PDX1 that are aberrantly divergent in amino acid sequence, whether they have also become divergent due to GC-biased nucleotide changes, and whether these proteins could plausibly be connected to metabolic dysfunction exhibited by gerbils. Results: We analyzed ~ 10,000 proteins with 1-to-1 orthologues in human and rodents and identified 50 proteins that accumulated unusually high levels of amino acid change in the sand rat and 41 in Mongolian jird. We show that more than half of the aberrantly divergent proteins are associated with GC biased nucleotide change and many are in previously defined high GC regions. We highlight four aberrantly divergent gerbil proteins, PDX1, INSR, MEDAG and SPP1, that may plausibly be associated with dietary metabolism.
    [Show full text]
  • Lampreys, the Jawless Vertebrates, Contain Only Two Parahox Gene Clusters
    Lampreys, the jawless vertebrates, contain only two ParaHox gene clusters Huixian Zhanga,b,1, Vydianathan Ravia,1, Boon-Hui Taya, Sumanty Toharia, Nisha E. Pillaia, Aravind Prasada, Qiang Linb, Sydney Brennera,2, and Byrappa Venkatesha,c,2 aInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Biopolis, Singapore 138673, Singapore; bChinese Academy of Sciences (CAS) Key Laboratory of Tropical Marine Bioresources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China; and cDepartment of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore Contributed by Sydney Brenner, July 6, 2017 (sent for review March 20, 2017; reviewed by José Luis Gómez-Skarmeta and Nipam H. Patel) ParaHox genes (Gsx, Pdx,andCdx) are an ancient family of develop- elephant shark, Callorhinchus milii; as well as the lobe-finned fish, mental genes closely related to the Hox genes. They play critical roles in coelacanth (Latimeria chalumnae), and spotted gar (Lepisosteus the patterning of brain and gut. The basal chordate, amphioxus, con- oculatus), a basal ray-finned fish (Actinopterygian), possess an ad- tains a single ParaHox cluster comprising one member of each family, ditional Pdx gene (called Pdx2)linkedtoGsx2 (Fig. 1) (8–10). In- whereas nonteleost jawed vertebrates contain four ParaHox genomic terestingly, teleosts that have experienced an additional round of loci with six or seven ParaHox genes. Teleosts, which have experienced genome duplication (3R) possess only six ParaHox genes distrib- an additional whole-genome duplication, contain six ParaHox genomic uted in six genomic loci (11, 12) (Fig. 1). As a consequence of the loci with six ParaHox genes.
    [Show full text]
  • Marletaz-2015-Cdx Parahox Genes Acquired Disti
    This is a repository copy of Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution. White Rose Research Online URL for this paper: https://eprints.whiterose.ac.uk/90983/ Version: Published Version Article: Marlétaz, Ferdinand, Maeso, Ignacio, Faas, Laura et al. (2 more authors) (2015) Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution. BMC Biology. p. 56. ISSN 1741-7007 https://doi.org/10.1186/s12915-015-0165-x Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless indicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by national copyright laws. The publisher or other rights holders may allow further reproduction and re-use of the full text version. This is indicated by the licence information on the White Rose Research Online record for the item. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ Marlétaz et al. BMC Biology (2015) 13:56 DOI 10.1186/s12915-015-0165-x RESEARCHARTICLE Open Access Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution Ferdinand Marlétaz1, Ignacio Maeso1,3, Laura Faas2, Harry V. Isaacs2 and Peter W. H. Holland1* Abstract Background: The functional consequences of whole genome duplications in vertebrate evolution are not fully understood.
    [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]
  • The Genetic Factors of Bilaterian Evolution Peter Heger1*, Wen Zheng1†, Anna Rottmann1, Kristen a Panfilio2,3, Thomas Wiehe1
    RESEARCH ARTICLE The genetic factors of bilaterian evolution Peter Heger1*, Wen Zheng1†, Anna Rottmann1, Kristen A Panfilio2,3, Thomas Wiehe1 1Institute for Genetics, Cologne Biocenter, University of Cologne, Cologne, Germany; 2Institute for Zoology: Developmental Biology, Cologne Biocenter, University of Cologne, Cologne, Germany; 3School of Life Sciences, University of Warwick, Gibbet Hill Campus, Coventry, United Kingdom Abstract The Cambrian explosion was a unique animal radiation ~540 million years ago that produced the full range of body plans across bilaterians. The genetic mechanisms underlying these events are unknown, leaving a fundamental question in evolutionary biology unanswered. Using large-scale comparative genomics and advanced orthology evaluation techniques, we identified 157 bilaterian-specific genes. They include the entire Nodal pathway, a key regulator of mesoderm development and left-right axis specification; components for nervous system development, including a suite of G-protein-coupled receptors that control physiology and behaviour, the Robo- Slit midline repulsion system, and the neurotrophin signalling system; a high number of zinc finger transcription factors; and novel factors that previously escaped attention. Contradicting the current view, our study reveals that genes with bilaterian origin are robustly associated with key features in extant bilaterians, suggesting a causal relationship. *For correspondence: [email protected] Introduction The taxon Bilateria consists of multicellular animals
    [Show full text]
  • PBX Proteins: Much More Than Hox Cofactors Audrey Laurent, Réjane Bihan, Francis Omilli, Stéphane Deschamps, Isabelle Pellerin
    PBX proteins: much more than Hox cofactors Audrey Laurent, Réjane Bihan, Francis Omilli, Stéphane Deschamps, Isabelle Pellerin To cite this version: Audrey Laurent, Réjane Bihan, Francis Omilli, Stéphane Deschamps, Isabelle Pellerin. PBX proteins: much more than Hox cofactors. International Journal of Developmental Biology, University of the Basque Country Press, 2008, 52 (1), pp.9-20. 10.1387/ijdb.072304al. hal-00278747 HAL Id: hal-00278747 https://hal.archives-ouvertes.fr/hal-00278747 Submitted on 11 Jul 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Int. J. Dev. Biol. 52: 9-20 (2008) DEVELOPMENTALTHE INTERNATIONAL JOURNAL OF doi: 10.1387/ijdb.072304al BIOLOGY www.intjdevbiol.com PBX proteins: much more than Hox cofactors AUDREY LAURENT, RÉJANE BIHAN, FRANCIS OMILLI, STÉPHANE DESCHAMPS and ISABELLE PELLERIN* IGDR, UMR CNRS 6061, Génétique et Développement, IFR 140, Faculté de Médecine, Université de Rennes 1, France ABSTRACT Pre-B cell leukaemia transcription factors (PBXs) were originally identified as Hox cofactors, acting within transcriptional regulation complexes to regulate genetic programs during development. Increasing amount of evidence revealed that PBX function is not restricted to a partnership with Hox or homeodomain proteins.
    [Show full text]
  • Logics and Properties of a Genetic Regulatory Program That Drives
    RESEARCH ARTICLE elifesciences.org Logics and properties of a genetic regulatory program that drives embryonic muscle development in an echinoderm Carmen Andrikou1†, Chih-Yu Pai2, Yi-Hsien Su2*, Maria Ina Arnone1* 1Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Napoli, Italy; 2Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan Abstract Evolutionary origin of muscle is a central question when discussing mesoderm evolution. Developmental mechanisms underlying somatic muscle development have mostly been studied in vertebrates and fly where multiple signals and hierarchic genetic regulatory cascades selectively specify myoblasts from a pool of naive mesodermal progenitors. However, due to the increased organismic complexity and distant phylogenetic position of the two systems, a general mechanistic understanding of myogenesis is still lacking. In this study, we propose a gene regulatory network (GRN) model that promotes myogenesis in the sea urchin embryo, an early branching deuterostome. A fibroblast growth factor signaling and four Forkhead transcription factors consist the central part of our model and appear to orchestrate the myogenic process. The topological properties of the network reveal dense gene interwiring and a multilevel transcriptional regulation of conserved and novel myogenic genes. Finally, the comparison of the myogenic network architecture among different animal groups highlights the evolutionary plasticity of developmental GRNs. *For correspondence: yhsu@ DOI: 10.7554/eLife.07343.001 gate.sinica.edu.tw (Y-HS); [email protected] (MIA) Present address: †Sars International Centre for Marine Molecular Biology, University of Introduction Bergen, Bergen, Norway Muscle cells are present in most animals with the characteristic of containing protein filaments that slide and produce contractions.
    [Show full text]
  • Insulin-Like Growth Factor 1 Is a Direct HOXA9 Target Important for Hematopoietic Transformation
    Leukemia (2015) 29, 901–908 © 2015 Macmillan Publishers Limited All rights reserved 0887-6924/15 www.nature.com/leu ORIGINAL ARTICLE Insulin-like growth factor 1 is a direct HOXA9 target important for hematopoietic transformation J Steger, E Füller, M-P Garcia-Cuellar, K Hetzner and RK Slany HOX homeobox proteins are key oncogenic drivers in hematopoietic malignancies. Here we demonstrate that HOXA1, HOXA6 and predominantly HOXA9 are able to induce the production of insulin-like growth factor 1 (Igf1). In chromatin immunoprecipitations, HOXA9 bound directly to the putative promoter and a DNase-hypersensitive region in the first intron of the Igf1 gene. Transcription rates of the Igf1 gene paralleled HOXA9 activity. Primary cells transformed by HOXA9 expressed functional Igf1 receptors and activated the protein kinase Akt in response to Igf1 stimulation, suggesting the existence of an autocrine signaling loop. Genomic deletion of the Igf1 gene by Cre-mediated recombination increased sensitivity toward apoptosis after serum starvation. In addition, the leukemogenic potential of Igf1-negative, HOXA9-transformed cells was impaired, leading to a significant delay in disease development on transplantation into recipient animals. Leukemia (2015) 29, 901–908; doi:10.1038/leu.2014.287 INTRODUCTION factor FGF2 (fibroblast growth factor) are regulated by HOX 14,15 HOX homeobox genes are increasingly acknowledged as impor- proteins. Apart from these examples and despite the tant drivers of malignant transformation in the hematopoietic discovery of numerous HOXA9-binding sites across the genome 16 system. In line with their major regulatory role in hematopoietic by chromatin immunoprecipitation-sequencing ChIP-Seq, func- stem and precursor cell populations, HOX transcription needs to tionally characterized HOX targets are scarce.
    [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]
  • Cdx Parahox Genes Acquired Distinct Developmental Roles After Gene Duplication in Vertebrate Evolution Ferdinand Marlétaz1, Ignacio Maeso1,3, Laura Faas2, Harry V
    Marlétaz et al. BMC Biology (2015) 13:56 DOI 10.1186/s12915-015-0165-x RESEARCH ARTICLE Open Access Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution Ferdinand Marlétaz1, Ignacio Maeso1,3, Laura Faas2, Harry V. Isaacs2 and Peter W. H. Holland1* Abstract Background: The functional consequences of whole genome duplications in vertebrate evolution are not fully understood. It remains unclear, for instance, why paralogues were retained in some gene families but extensively lost in others. Cdx homeobox genes encode conserved transcription factors controlling posterior development across diverse bilaterians. These genes are part of the ParaHox gene cluster. Multiple Cdx copies were retained after genome duplication, raising questions about how functional divergence, overlap, and redundancy respectively contributed to their retention and evolutionary fate. Results: We examined the degree of regulatory and functional overlap between the three vertebrate Cdx genes using single and triple morpholino knock-down in Xenopus tropicalis followed by RNA-seq. We found that one paralogue, Cdx4, has a much stronger effect on gene expression than the others, including a strong regulatory effect on FGF and Wnt genes. Functional annotation revealed distinct and overlapping roles and subtly different temporal windows of action for each gene. The data also reveal a colinear-like effect of Cdx genes on Hox genes, with repression of Hox paralogy groups 1 and 2, and activation increasing from Hox group 5 to 11. We also highlight cases in which duplicated genes regulate distinct paralogous targets revealing pathway elaboration after whole genome duplication. Conclusions: Despite shared core pathways, Cdx paralogues have acquired distinct regulatory roles during development.
    [Show full text]
  • Evolution of Antp-Class Genes and Differential Expression of Hydra Hox͞parahox Genes in Anterior Patterning
    Evolution of Antp-class genes and differential expression of Hydra Hox͞paraHox genes in anterior patterning Dominique Gauchat*, Franc¸oise Mazet*, Ce´ dric Berney*†, Miche` l Schummer‡§, Sylvia Kreger‡, Jan Pawlowski*†, and Brigitte Galliot*¶ Department of Zoology and Animal Biology, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland; †Station de Zoologie, 154 Route de Malagnou, CH-1224 Cheˆne-Bougeries, Switzerland; and ‡Zentrum fu¨r Molecular Biologie, University of Heidelberg, INF 282, D-69120 Heidelberg, Germany Edited by Walter J. Gehring, University of Basel, Basel, Switzerland, and approved February 22, 2000 (received for review January 5, 2000) The conservation of developmental functions exerted by Antp- the Dfd-like and the Antp-like genes (PG-4͞6), and a 3Ј located class homeoproteins in protostomes and deuterostomes suggested gene ancestral for the pb- and lab-like genes (PG-1͞2). A similar that homologs with related functions are present in diploblastic organization of the evolutionary sister of the HOX cluster, the animals. Our phylogenetic analyses showed that Antp-class home- paraHOX cluster, was actually observed in amphioxus (11). odomains belong either to non-Hox or to Hox͞paraHox families. However, analysis of a more complete set of HD sequences led Among the 13 non-Hox families, 9 have diploblastic homologs, to the hypothesis that an original and ancient split, rather, Msx, Emx, Barx, Evx, Tlx, NK-2, and Prh͞Hex, Not, and Dlx, reported occurred between the anterior and posterior Hox genes, which here. Among the Hox͞paraHox, poriferan sequences were not later on duplicated separately (12). found, and the cnidarian sequences formed at least five distinct Because the Cnidaria can be regarded as the sister group to the cnox families.
    [Show full text]