Genetically Regulated Human NODAL Splice Variants Are Differentially Post-Transcriptionally Processed and Functionally Distinct
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Spemann Organizer Transcriptome Induction by Early Beta-Catenin, Wnt
Spemann organizer transcriptome induction by early PNAS PLUS beta-catenin, Wnt, Nodal, and Siamois signals in Xenopus laevis Yi Dinga,b,1, Diego Plopera,b,1, Eric A. Sosaa,b, Gabriele Colozzaa,b, Yuki Moriyamaa,b, Maria D. J. Beniteza,b, Kelvin Zhanga,b, Daria Merkurjevc,d,e, and Edward M. De Robertisa,b,2 aHoward Hughes Medical Institute, University of California, Los Angeles, CA 90095-1662; bDepartment of Biological Chemistry, University of California, Los Angeles, CA 90095-1662; cDepartment of Medicine, University of California, Los Angeles, CA 90095-1662; dDepartment of Microbiology, University of California, Los Angeles, CA 90095-1662; and eDepartment of Human Genetics, University of California, Los Angeles, CA 90095-1662 Contributed by Edward M. De Robertis, February 24, 2017 (sent for review January 17, 2017; reviewed by Juan Larraín and Stefano Piccolo) The earliest event in Xenopus development is the dorsal accumu- Wnt8 mRNA leads to a dorsalized phenotype consisting entirely of lation of nuclear β-catenin under the influence of cytoplasmic de- head structures without trunks and a radial Spemann organizer terminants displaced by fertilization. In this study, a genome-wide (9–11). Similar dorsalizing effects are obtained by incubating approach was used to examine transcription of the 43,673 genes embryos in lithium chloride (LiCl) solution at the 32-cell stage annotated in the Xenopus laevis genome under a variety of con- (12). LiCl mimics the early Wnt signal by inhibiting the enzymatic ditions that inhibit or promote formation of the Spemann orga- activity of glycogen synthase kinase 3 (GSK3) (13), an enzyme nizer signaling center. -
Cripto-1 As a Potential Target of Cancer Stem Cells for Immunotherapy
cancers Review Cripto-1 as a Potential Target of Cancer Stem Cells for Immunotherapy Hiroko Ishii 1 , Said M. Afify 2,3 , Ghmkin Hassan 2 , David S. Salomon 4 and Masaharu Seno 2,* 1 GSP Enterprise, Inc., 1-4-38 12F Minato-machi, Naniwa-ku, Osaka 556-0017, Japan; [email protected] 2 Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, Japan; saidafi[email protected] (S.M.A.); [email protected] (G.H.) 3 Division of Biochemistry, Chemistry Department, Faculty of Science, Menoufia University, Shebin ElKoum Menoufia 32511, Egypt 4 Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; [email protected] * Correspondence: [email protected]; Tel.: +81-86-251-8216 Simple Summary: Cancer immunotherapy is gaining attention as a potential fourth treatment following surgery, chemotherapy, and radiation therapy. Cancer stem cells have recently been recognized and validated as a key target for cancer treatment. Cripto-1, which is a GPI-anchored membrane-bound protein that functions as a co-receptor of Nodal, is a marker of cancer stem cells. Since Nodal is a member of the TGF-β family, which performs an important role in stem cells and cancer stem cells, the inhibition of Cripto-1 could be a strategy by which to block Nodal signaling and thereby suppress cancer stem cells. We propose that Cripto-1 may be a novel target for cancer immunotherapy. Citation: Ishii, H.; Afify, S.M.; Hassan, G.; Salomon, D.S.; Seno, M. -
Structure of Protein Related to Dan and Cerberus: Insights Into the Mechanism of Bone Morphogenetic Protein Antagonism
Structure Article Structure of Protein Related to Dan and Cerberus: Insights into the Mechanism of Bone Morphogenetic Protein Antagonism Kristof Nolan,1,5 Chandramohan Kattamuri,1,5 David M. Luedeke,1 Xiaodi Deng,1 Amrita Jagpal,2 Fuming Zhang,3 Robert J. Linhardt,3,4 Alan P. Kenny,2 Aaron M. Zorn,2 and Thomas B. Thompson1,* 1Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Medical Sciences Building, Cincinnati, OH 45267, USA 2Perinatal Institute, Cincinnati Children’s Research Foundation and Department of Pediatrics, College of Medicine, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA 3Departments of Chemical and Biological Engineering and Chemistry and Chemical Biology 4Departments of Biology and Biomedical Engineering Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA 5These authors contributed equally to this work *Correspondence: [email protected] http://dx.doi.org/10.1016/j.str.2013.06.005 SUMMARY follicular development, as well as gut differentiation from meso- derm tissue (Bragdon et al., 2011). Furthermore, their roles in The bone morphogenetic proteins (BMPs) are several disease states, including lung and kidney fibrosis, oste- secreted ligands largely known for their functional oporosis, and cardiovascular disease, have indicated their roles in embryogenesis and tissue development. A importance in adult homeostasis (Cai et al., 2012; Walsh et al., number of structurally diverse extracellular antago- 2010). nists inhibit BMP ligands to regulate signaling. The At the molecular level, BMP ligands form stable disulfide- differential screening-selected gene aberrative in bonded dimers that transduce their signals by binding two type I and two type II receptors, leading to type I receptor phos- neuroblastoma (DAN) family of antagonists repre- phorylation. -
Evolutionary Origin of Bone Morphogenetic Protein 15 And
Evolutionary origin of Bone Morphogenetic Protein 15 and growth and differentiation factor 9 and differential selective pressure between mono- and polyovulating species Olivier Monestier, Bertrand Servin, Sylvain Auclair, Thomas Bourquard, Anne Poupon, Géraldine Pascal, Stéphane Fabre To cite this version: Olivier Monestier, Bertrand Servin, Sylvain Auclair, Thomas Bourquard, Anne Poupon, et al.. Evo- lutionary origin of Bone Morphogenetic Protein 15 and growth and differentiation factor 9 and differ- ential selective pressure between mono- and polyovulating species. Biology of Reproduction, Society for the Study of Reproduction, 2014, 91 (4), pp.1-13. 10.1095/biolreprod.114.119735. hal-01129871 HAL Id: hal-01129871 https://hal.archives-ouvertes.fr/hal-01129871 Submitted on 27 May 2020 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. BIOLOGY OF REPRODUCTION (2014) 91(4):83, 1–13 Published online before print 6 August 2014. DOI 10.1095/biolreprod.114.119735 Evolutionary Origin of Bone Morphogenetic Protein 15 and Growth and Differentiation Factor 9 -
Mouse GDF-8/Myostatin Propeptide Antibody
Mouse GDF-8/Myostatin Propeptide Antibody Monoclonal Rat IgG2B Clone # 84231 Catalog Number: MAB7881 DESCRIPTION Species Reactivity Mouse Specificity Detects mouse GDF8 propeptide in direct ELISAs and Western blots. In direct ELISAs, no crossreactivity with recombinant mouse (rm) GDF1 propeptide, rmGDF3 propeptide, rmGDF5, or rmGDF6 is observed. Source Monoclonal Rat IgG2B Clone # 84231 Purification Protein A or G purified from hybridoma culture supernatant Immunogen Mouse myeloma cell line NS0derived recombinant mouse GDF8 Asn25Ser376 Accession # O08689 Formulation Lyophilized from a 0.2 μm filtered solution in PBS with Trehalose. See Certificate of Analysis for details. *Small pack size (SP) is supplied either lyophilized or as a 0.2 μm filtered solution in PBS. APPLICATIONS Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website. Recommended Sample Concentration Western Blot 1 µg/mL Recombinant Mouse GDF8/Myostatin Propeptide (Catalog # 1539PG) PREPARATION AND STORAGE Reconstitution Reconstitute at 0.5 mg/mL in sterile PBS. Shipping The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature recommended below. *Small pack size (SP) is shipped with polar packs. Upon receipt, store it immediately at 20 to 70 °C Stability & Storage Use a manual defrost freezer and avoid repeated freezethaw cycles. l 12 months from date of receipt, 20 to 70 °C as supplied. l 1 month, 2 to 8 °C under sterile conditions after reconstitution. l 6 months, 20 to 70 °C under sterile conditions after reconstitution. -
GDF11 in Ocular Development and MOTA Mapping by Robertino Ralph Karlo Peralta Mateo
University of Alberta GDF11 in Ocular Development and MOTA Mapping by Robertino Ralph Karlo Peralta Mateo A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science In Medical Sciences – Medical Genetics ©Robertino Ralph Karlo Peralta Mateo Fall 2012 Edmonton, Alberta Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission. Abstract Vision relies on the ability of the eye to receive, process, and send signals to the brain for interpretation. To perform these functions, the eye must properly form during embryogenesis which requires the interaction of genes encoding proteins with various functions during development such as cellular differentiation, migration, and proliferation. In this thesis, I investigate ocular formation and disease. One project assesses the role of gdf11 in a zebrafish animal model to study the eye formation. I also explore the effect of human GDF11 sequence variants in ocular disorders. The second project involves mapping a genomic interval responsible for an autosomal recessive disorder known as Manitoba Oculotrichoanal syndrome. -
Amh) Relative to Sox9a, Sox9b, and Cyp19a1a, During Gonad Development
Gene Expression Patterns 5 (2005) 655–667 www.elsevier.com/locate/modgep Characterization and expression pattern of zebrafish anti-Mu¨llerian hormone (amh) relative to sox9a, sox9b, and cyp19a1a, during gonad development Adriana Rodrı´guez-Marı´, Yi-Lin Yan, Ruth A. BreMiller, Catherine Wilson, Cristian Can˜estro, John H. Postlethwait* Institute of Neuroscience, University of Oregon, 1425 E. 13th Avenue, Eugene, OR 97403, USA Received 28 January 2005; received in revised form 28 February 2005; accepted 28 February 2005 Available online 19 April 2005 Abstract The role of Anti-Mu¨llerian hormone (Amh) during gonad development has been studied extensively in mammals, but is less well understood in other vertebrates. In male mammalian embryos, Sox9 activates expression of Amh, which initiates the regression of the Mu¨llerian ducts and inhibits the expression of aromatase (Cyp19a1), the enzyme that converts androgens to estrogens. To better understand shared features of vertebrate gonadogenesis, we cloned amh cDNA from zebrafish, characterized its genomic structure, mapped it, analyzed conserved syntenies, studied its expression pattern in embryos, larvae, juveniles, and adults, and compared it to the expression patterns of sox9a, sox9b and cyp19a1a. We found that the onset of amh expression occurred while gonads were still undifferentiated and sox9a and cyp19a1a were already expressed. In differentiated gonads of juveniles, amh showed a sexually dimorphic expression pattern. In 31 days post-fertilization juveniles, testes expressed amh and sox9a, but not cyp19a1a, while ovaries expressed cyp19a1a and sox9b, but not amh.In adult testes, amh and sox9a were expressed in presumptive Sertoli cells. In adult ovaries, amh and cyp19a1a were expressed in granulosa cells surrounding the oocytes, and sox9b was expressed in a complementary fashion in the ooplasm of oocytes. -
Integrative Differential Expression and Gene Set Enrichment Analysis Using Summary Statistics for Scrna-Seq Studies
ARTICLE https://doi.org/10.1038/s41467-020-15298-6 OPEN Integrative differential expression and gene set enrichment analysis using summary statistics for scRNA-seq studies ✉ Ying Ma 1,7, Shiquan Sun 1,7, Xuequn Shang2, Evan T. Keller 3, Mengjie Chen 4,5 & Xiang Zhou 1,6 Differential expression (DE) analysis and gene set enrichment (GSE) analysis are commonly applied in single cell RNA sequencing (scRNA-seq) studies. Here, we develop an integrative 1234567890():,; and scalable computational method, iDEA, to perform joint DE and GSE analysis through a hierarchical Bayesian framework. By integrating DE and GSE analyses, iDEA can improve the power and consistency of DE analysis and the accuracy of GSE analysis. Importantly, iDEA uses only DE summary statistics as input, enabling effective data modeling through com- plementing and pairing with various existing DE methods. We illustrate the benefits of iDEA with extensive simulations. We also apply iDEA to analyze three scRNA-seq data sets, where iDEA achieves up to five-fold power gain over existing GSE methods and up to 64% power gain over existing DE methods. The power gain brought by iDEA allows us to identify many pathways that would not be identified by existing approaches in these data. 1 Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA. 2 School of Computer Science, Northwestern Polytechnical University, Xi’an, Shaanxi 710072, P.R. China. 3 Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA. 4 Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. 5 Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. -
Supplemental Table 1. Complete Gene Lists and GO Terms from Figure 3C
Supplemental Table 1. Complete gene lists and GO terms from Figure 3C. Path 1 Genes: RP11-34P13.15, RP4-758J18.10, VWA1, CHD5, AZIN2, FOXO6, RP11-403I13.8, ARHGAP30, RGS4, LRRN2, RASSF5, SERTAD4, GJC2, RHOU, REEP1, FOXI3, SH3RF3, COL4A4, ZDHHC23, FGFR3, PPP2R2C, CTD-2031P19.4, RNF182, GRM4, PRR15, DGKI, CHMP4C, CALB1, SPAG1, KLF4, ENG, RET, GDF10, ADAMTS14, SPOCK2, MBL1P, ADAM8, LRP4-AS1, CARNS1, DGAT2, CRYAB, AP000783.1, OPCML, PLEKHG6, GDF3, EMP1, RASSF9, FAM101A, STON2, GREM1, ACTC1, CORO2B, FURIN, WFIKKN1, BAIAP3, TMC5, HS3ST4, ZFHX3, NLRP1, RASD1, CACNG4, EMILIN2, L3MBTL4, KLHL14, HMSD, RP11-849I19.1, SALL3, GADD45B, KANK3, CTC- 526N19.1, ZNF888, MMP9, BMP7, PIK3IP1, MCHR1, SYTL5, CAMK2N1, PINK1, ID3, PTPRU, MANEAL, MCOLN3, LRRC8C, NTNG1, KCNC4, RP11, 430C7.5, C1orf95, ID2-AS1, ID2, GDF7, KCNG3, RGPD8, PSD4, CCDC74B, BMPR2, KAT2B, LINC00693, ZNF654, FILIP1L, SH3TC1, CPEB2, NPFFR2, TRPC3, RP11-752L20.3, FAM198B, TLL1, CDH9, PDZD2, CHSY3, GALNT10, FOXQ1, ATXN1, ID4, COL11A2, CNR1, GTF2IP4, FZD1, PAX5, RP11-35N6.1, UNC5B, NKX1-2, FAM196A, EBF3, PRRG4, LRP4, SYT7, PLBD1, GRASP, ALX1, HIP1R, LPAR6, SLITRK6, C16orf89, RP11-491F9.1, MMP2, B3GNT9, NXPH3, TNRC6C-AS1, LDLRAD4, NOL4, SMAD7, HCN2, PDE4A, KANK2, SAMD1, EXOC3L2, IL11, EMILIN3, KCNB1, DOK5, EEF1A2, A4GALT, ADGRG2, ELF4, ABCD1 Term Count % PValue Genes regulation of pathway-restricted GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, SMAD protein phosphorylation 9 6.34 1.31E-08 ENG pathway-restricted SMAD protein GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, phosphorylation -
Follistatin and Noggin Are Excluded from the Zebrafish Organizer
DEVELOPMENTAL BIOLOGY 204, 488–507 (1998) ARTICLE NO. DB989003 Follistatin and Noggin Are Excluded from the Zebrafish Organizer Hermann Bauer,* Andrea Meier,* Marc Hild,* Scott Stachel,†,1 Aris Economides,‡ Dennis Hazelett,† Richard M. Harland,† and Matthias Hammerschmidt*,2 *Max-Planck Institut fu¨r Immunbiologie, Stu¨beweg 51, 79108 Freiburg, Germany; †Department of Molecular and Cell Biology, University of California, 401 Barker Hall 3204, Berkeley, California 94720-3204; and ‡Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707 The patterning activity of the Spemann organizer in early amphibian embryos has been characterized by a number of organizer-specific secreted proteins including Chordin, Noggin, and Follistatin, which all share the same inductive properties. They can neuralize ectoderm and dorsalize ventral mesoderm by blocking the ventralizing signals Bmp2 and Bmp4. In the zebrafish, null mutations in the chordin gene, named chordino, lead to a severe reduction of organizer activity, indicating that Chordino is an essential, but not the only, inductive signal generated by the zebrafish organizer. A second gene required for zebrafish organizer function is mercedes, but the molecular nature of its product is not known as yet. To investigate whether and how Follistatin and Noggin are involved in dorsoventral (D-V) patterning of the zebrafish embryo, we have now isolated and characterized their zebrafish homologues. Overexpression studies demonstrate that both proteins have the same dorsalizing properties as their Xenopus homologues. However, unlike the Xenopus genes, zebrafish follistatin and noggin are not expressed in the organizer region, nor are they linked to the mercedes mutation. Expression of both genes starts at midgastrula stages. -
The Novel Cer-Like Protein Caronte Mediates the Establishment of Embryonic Left±Right Asymmetry
articles The novel Cer-like protein Caronte mediates the establishment of embryonic left±right asymmetry ConcepcioÂn RodrõÂguez Esteban*², Javier Capdevila*², Aris N. Economides³, Jaime Pascual§,AÂ ngel Ortiz§ & Juan Carlos IzpisuÂa Belmonte* * The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla, California 92037, USA ³ Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York 10591, USA § Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA ² These authors contributed equally to this work ............................................................................................................................................................................................................................................................................ In the chick embryo, left±right asymmetric patterns of gene expression in the lateral plate mesoderm are initiated by signals located in and around Hensen's node. Here we show that Caronte (Car), a secreted protein encoded by a member of the Cerberus/ Dan gene family, mediates the Sonic hedgehog (Shh)-dependent induction of left-speci®c genes in the lateral plate mesoderm. Car is induced by Shh and repressed by ®broblast growth factor-8 (FGF-8). Car activates the expression of Nodal by antagonizing a repressive activity of bone morphogenic proteins (BMPs). Our results de®ne a complex network of antagonistic molecular interactions between Activin, FGF-8, Lefty-1, Nodal, BMPs and Car that cooperate to control left±right asymmetry in the chick embryo. Many of the cellular and molecular events involved in the establish- If the initial establishment of asymmetric gene expression in the ment of left±right asymmetry in vertebrates are now understood. LPM is essential for proper development, it is equally important to Following the discovery of the ®rst genes asymmetrically expressed ensure that asymmetry is maintained throughout embryogenesis. -
Nodal Signaling Is Required for Mesodermal and Ventral but Not For
© 2015. Published by The Company of Biologists Ltd | Biology Open (2015) 4, 830-842 doi:10.1242/bio.011809 RESEARCH ARTICLE Nodal signaling is required for mesodermal and ventral but not for dorsal fates in the indirect developing hemichordate, Ptychodera flava Eric Röttinger1,2,3,*, Timothy Q. DuBuc4, Aldine R. Amiel1,2,3 and Mark Q. Martindale4 ABSTRACT early fate maps of direct and indirect developing hemichordates, are Nodal signaling plays crucial roles in vertebrate developmental similar to those of indirect-developing echinoids (Colwin and processes such as endoderm and mesoderm formation, and axial Colwin, 1951; Cameron et al., 1987; Cameron et al., 1989; Cameron patterning events along the anteroposterior, dorsoventral and left- and Davidson, 1991; Henry et al., 2001). While the bilaterally right axes. In echinoderms, Nodal plays an essential role in the symmetric echinoderm larvae exhibit strong similarities to establishment of the dorsoventral axis and left-right asymmetry, but chordates in axial patterning and germ layer specification events, not in endoderm or mesoderm induction. In protostomes, Nodal adult body plan comparisons in echinoderms have been difficult due signaling appears to be involved only in establishing left-right to their unique adult pentaradial symmetry. However, both the larval asymmetry. Hence, it is hypothesized that Nodal signaling has and adult body plans of enteropneust hemichordates are bilaterally been co-opted to pattern the dorsoventral axis of deuterostomes and symmetric, and larvae from indirect developing hemichordates for endoderm, mesoderm formation as well as anteroposterior such as Ptychodera flava (P. flava) share similarities in patterning in chordates. Hemichordata, together with echinoderms, morphology, axial organization, and developmental fate map with represent the sister taxon to chordates.