{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T19:38:31Z","timestamp":1777491511996,"version":"3.51.4"},"reference-count":96,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:00:00Z","timestamp":1592265600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:00:00Z","timestamp":1592265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Elizabeth Hannah Jenkinson Fund"},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["BFU2017-86152-P"],"award-info":[{"award-number":["BFU2017-86152-P"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016270","name":"Global Challenges Research Fund","doi-asserted-by":"crossref","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100016270","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31872186"],"award-info":[{"award-number":["31872186"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["20720160056"],"award-info":[{"award-number":["20720160056"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Biol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The homeobox genes <jats:italic>Pdx<\/jats:italic> and <jats:italic>Cdx<\/jats:italic> are widespread across the animal kingdom and part of the small ParaHox gene cluster. Gene expression patterns suggest ancient roles for <jats:italic>Pdx<\/jats:italic> and <jats:italic>Cdx<\/jats:italic> in patterning the through-gut of bilaterian animals although functional data are available for few lineages. To examine evolutionary conservation of <jats:italic>Pdx<\/jats:italic> and <jats:italic>Cdx<\/jats:italic> gene functions, we focus on amphioxus, small marine animals that occupy a pivotal position in chordate evolution and in which ParaHox gene clustering was first reported.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Using transcription activator-like effector nucleases (TALENs), we engineer frameshift mutations in the <jats:italic>Pdx<\/jats:italic> and <jats:italic>Cdx<\/jats:italic> genes of the amphioxus <jats:italic>Branchiostoma floridae<\/jats:italic> and establish mutant lines. Homozygous <jats:italic>Pdx<\/jats:italic> mutants have a defect in amphioxus endoderm, manifest as loss of a midgut region expressing endogenous GFP. The anus fails to open in homozygous <jats:italic>Cdx<\/jats:italic> mutants, which also have defects in posterior body extension and epidermal tail fin development. Treatment with an inverse agonist of retinoic acid (RA) signalling partially rescues the axial and tail fin phenotypes indicating they are caused by increased RA signalling. Gene expression analyses and luciferase assays suggest that posterior RA levels are kept low in wild type animals by a likely direct transcriptional regulation of a <jats:italic>Cyp26<\/jats:italic> gene by Cdx. Transcriptome analysis reveals extensive gene expression changes in mutants, with a disproportionate effect of <jats:italic>Pdx<\/jats:italic> and <jats:italic>Cdx<\/jats:italic> on gut-enriched genes and a colinear-like effect of <jats:italic>Cdx<\/jats:italic> on Hox genes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These data reveal that amphioxus <jats:italic>Pdx<\/jats:italic> and <jats:italic>Cdx<\/jats:italic> have roles in specifying middle and posterior cell fates in the endoderm of the gut, roles that likely date to the origin of Bilateria. This conclusion is consistent with these two ParaHox genes playing a role in the origin of the bilaterian through-gut with a distinct anus, morphological innovations that contributed to ecological change in the Cambrian. In addition, we find that amphioxus <jats:italic>Cdx<\/jats:italic> promotes body axis extension through a molecular mechanism conserved with vertebrates. The axial extension role for <jats:italic>Cdx<\/jats:italic> dates back at least to the origin of Chordata and may have facilitated the evolution of the post-anal tail and active locomotion in chordates.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12915-020-00796-2","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T11:03:14Z","timestamp":1592305394000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Mutation of amphioxus Pdx and Cdx demonstrates conserved roles for ParaHox genes in gut, anus and tail patterning"],"prefix":"10.1186","volume":"18","author":[{"given":"Yanhong","family":"Zhong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Herrera-\u00dabeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Garcia-Fern\u00e0ndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1533-9376","authenticated-orcid":false,"given":"Peter W. H.","family":"Holland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,16]]},"reference":[{"key":"796_CR1","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1038\/31933","volume":"392","author":"NM Brooke","year":"1998","unstructured":"Brooke NM, Garcia-Fern\u00e0ndez J, Holland PWH. The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster. Nature. 1998;392:920\u20132.","journal-title":"Nature"},{"key":"796_CR2","doi-asserted-by":"publisher","first-page":"R820","DOI":"10.1016\/j.cub.2005.10.014","volume":"15","author":"DEK Ferrier","year":"2005","unstructured":"Ferrier DEK, Dewar K, Cook A, Chang JL, Hill-Force A, Amemiya C. The chordate ParaHox cluster. Curr Biol. 2005;15:R820\u20132.","journal-title":"Curr Biol"},{"key":"796_CR3","doi-asserted-by":"publisher","first-page":"10369","DOI":"10.1073\/pnas.0600341103","volume":"103","author":"JF Mulley","year":"2006","unstructured":"Mulley JF, Chiu C-H, Holland PWH. Breakup of a homeobox cluster after genome duplication in teleosts. PNAS. 2006;103:10369\u201372.","journal-title":"PNAS"},{"key":"796_CR4","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1002\/dvdy.21816","volume":"238","author":"JC Illes","year":"2009","unstructured":"Illes JC, Winterbottom E, Isaacs HV. Cloning and expression analysis of the anterior ParaHox genes Gsh1 and Gsh2 from Xenopus tropicalis. Devel Dynamics. 2009;238:194\u2013203.","journal-title":"Devel Dynamics"},{"key":"796_CR5","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/1741-7007-11-68","volume":"11","author":"R Annunziata","year":"2013","unstructured":"Annunziata R, Martinez P, Arnone MI. Intact cluster and chordate-like expression of ParaHox genes in a sea star. BMC Biol. 2013;11:68.","journal-title":"BMC Biol"},{"key":"796_CR6","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/1471-2148-13-129","volume":"13","author":"T Ikuta","year":"2013","unstructured":"Ikuta T, Chen Y-C, Anunziata R, Ting H-C, Tung CH, Koyanagi R, Tagawa K, Humphreys T, Fujiyama A, Saiga H, Satoh N, Yu J-K, Arnone MI, Su Y-H. Identification of an intact ParaHox cluster with temporal colinearity but residual spatial colinearity in the hemichordate Ptychodera flava. BMC Evol Biol. 2013;13:129.","journal-title":"BMC Evol Biol"},{"key":"796_CR7","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40851-016-0039-2","volume":"2","author":"T Takeuchi","year":"2016","unstructured":"Takeuchi T, Koyanagi R, Gyoja F, Kanda M, Hisata K, Fujie M, Goto H, Yamasaki S, Nagai K, Morino Y, Miyamoto H, et al. Bivalve-specific gene expansion in the pearl oyster genome: implications of adaptation to a sessile lifestyle. Zoological Lett. 2016;2:3.","journal-title":"Zoological Lett"},{"key":"796_CR8","doi-asserted-by":"publisher","first-page":"0120","DOI":"10.1038\/s41559-017-0120","volume":"1","author":"S Wang","year":"2017","unstructured":"Wang S, Zhang J, Jiao W, Li J, Xun X, Sun Y, Guo X, Huan P, Dong B, Zhang L, Hu X, et al. Scallop genome provides insights into evolution of bilaterian karyotype and development. Nature Ecol Evol. 2017;1:0120.","journal-title":"Nature Ecol Evol"},{"key":"796_CR9","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/1741-7007-7-43","volume":"7","author":"JH Hui","year":"2009","unstructured":"Hui JH, Raible F, Korchagina N, Dray N, Samain S, Magdelenat G, Jubin C, Segurens B, Balavoine G, Arendt D, Ferrier DEK. Features of the ancestral bilaterian inferred from Platynereis dumerilii ParaHox genes. BMC Biol. 2009;7:43.","journal-title":"BMC Biol"},{"key":"796_CR10","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/1741-7007-11-72","volume":"11","author":"M Garstang","year":"2013","unstructured":"Garstang M, Ferrier DEK. Time is of the essence for ParaHox gene clustering. BMC Biol. 2013;11:72.","journal-title":"BMC Biol"},{"key":"796_CR11","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1242\/dev.105.4.787","volume":"105","author":"CVE Wright","year":"1988","unstructured":"Wright CVE, Schnegelsberg P, De Robertis EM. XlHbox 8: a novel Xenopus homeo protein restricted to a narrow band of endoderm. Development. 1988;105:787\u201394.","journal-title":"Development"},{"key":"796_CR12","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1242\/dev.122.3.983","volume":"122","author":"MF Offield","year":"1996","unstructured":"Offield MF, Jetton TL, Labosky PA, Ray M, Stein RW, Magnuson MA, Hogan BLM, Wright CVE. PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development. 1996;122:983\u201395.","journal-title":"Development"},{"key":"796_CR13","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1387\/ijdb.120048ah","volume":"57","author":"AM Holland","year":"2013","unstructured":"Holland AM, Garcia S, Naselli G, MacDonald RJ, Harrison LC. The Parahox gene Pdx1 is required to maintain positional identity in the adult foregut. Int J Devel Biol. 2013;57:391\u20138.","journal-title":"Int J Devel Biol"},{"key":"796_CR14","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.ydbio.2008.11.027","volume":"327","author":"PW Osborne","year":"2009","unstructured":"Osborne PW, Benoit G, Laudet V, Schubert M, Ferrier DEK. Differential regulation of ParaHox genes by retinoic acid in the invertebrate chordate amphioxus (Branchiostoma floridae). Devel Biology. 2009;327:252\u201362.","journal-title":"Devel Biology"},{"key":"796_CR15","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1101\/gr.076208.108","volume":"18","author":"JK Yu","year":"2008","unstructured":"Yu JK, Meulemans D, McKeown SJ, Bronner-Fraser M. Insights from the amphioxus genome on the origin of vertebrate neural crest. Genome Res. 2008;18:1127\u201332.","journal-title":"Genome Res"},{"key":"796_CR16","doi-asserted-by":"crossref","unstructured":"Lacalli T, Stach T. Acrania (Cepahlochordata). In: Structure and evolution of invertebrate nervous systems (Schmidt-Rhaesa A, Harzsch S, Purschke G eds.) Oxford University Press, Oxford. 2016; pp 719\u2013728.","DOI":"10.1093\/acprof:oso\/9780199682201.003.0054"},{"key":"796_CR17","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1002\/aja.1002040302","volume":"204","author":"F Beck","year":"1995","unstructured":"Beck F, Erler T, Russell A, James R. Expression of Cdx-2 in the mouse embryo and placenta: possible role in patterning of the extra-embryonic membranes. Devel Dyn. 1995;204:219\u201327.","journal-title":"Devel Dyn"},{"key":"796_CR18","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1242\/dev.129.9.2181","volume":"129","author":"E van den Akker","year":"2002","unstructured":"van den Akker E, Forlani S, Chawengsaksophak K, de Graaff W, Beck F, Meyer BI, Deschamps J. Cdx1 and Cdx2 have overlapping functions in anteroposterior patterning and posterior axis elongation. Development. 2002;129:2181\u201393.","journal-title":"Development"},{"key":"796_CR19","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s12915-015-0165-x","volume":"13","author":"F Marl\u00e9taz","year":"2015","unstructured":"Marl\u00e9taz F, Maeso I, Faas L, Isaacs HV, Holland PWH. Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution. BMC Biol. 2015;13:56.","journal-title":"BMC Biol"},{"key":"796_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40851-014-0004-x","volume":"1","author":"PWH Holland","year":"2015","unstructured":"Holland PWH. Did homeobox gene duplications contribute to the Cambrian explosion? Zoological Lett. 2015;1:1.","journal-title":"Zoological Lett"},{"key":"796_CR21","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1038\/nrg1723","volume":"6","author":"J Garcia-Fern\u00e0ndez","year":"2005","unstructured":"Garcia-Fern\u00e0ndez J. The genesis and evolution of homeobox gene clusters. Nature Rev Gen. 2005;6:881\u201392.","journal-title":"Nature Rev Gen"},{"key":"796_CR22","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1242\/dev.029959","volume":"136","author":"AG Cole","year":"2009","unstructured":"Cole AG, Rizzo F, Martinez P, Fernandez-Serra M, Arnone MI. Two ParaHox genes, SpLox and SpCdx, interact to partition the posterior endoderm in the formation of a functional gut. Development. 2009;136:541\u20139.","journal-title":"Development"},{"key":"796_CR23","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/1471-213X-10-74","volume":"10","author":"L Samadi","year":"2010","unstructured":"Samadi L, Steiner G. Conservation of ParaHox genes\u2019 function in patterning of the digestive tract of the marine gastropod Gibbula varia. BMC Devel Biol. 2010;10:74.","journal-title":"BMC Devel Biol"},{"key":"796_CR24","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1093\/icb\/38.6.829","volume":"38","author":"PWH Holland","year":"1998","unstructured":"Holland PWH. Major transitions in animal evolution: a developmental genetic perspective. Amer Zool. 1998;38:829\u201342.","journal-title":"Amer Zool"},{"key":"796_CR25","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.jcz.2015.02.006","volume":"256","author":"A Hejnol","year":"2015","unstructured":"Hejnol A, Mart\u00edn-Dur\u00e1n JM. Getting to the bottom of anal evolution. Zool Anz. 2015;256:61\u201374.","journal-title":"Zool Anz"},{"key":"796_CR26","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/371606a0","volume":"371","author":"J Jonsson","year":"1994","unstructured":"Jonsson J, Carlsson L, Edlund T, Edlund H. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature. 1994;371:606\u20139.","journal-title":"Nature"},{"key":"796_CR27","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/ng0197-106","volume":"15","author":"DA Stoffers","year":"1997","unstructured":"Stoffers DA, Zinkin NT, Stanojevic V, Clarke WL, Habener JF. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nature Genet. 1997;15:106\u201310.","journal-title":"Nature Genet"},{"key":"796_CR28","doi-asserted-by":"publisher","first-page":"4398","DOI":"10.1210\/jc.2003-030046","volume":"88","author":"VM Schwitzgebel","year":"2003","unstructured":"Schwitzgebel VM, Mamin A, Brun T, Ritz-Laser B, Zaiko M, Maret A, Jornayvaz FR, Theintz GE, Michielin O, Melloul D, Philippe J. Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1. J Clin Endocrinology & Metab. 2003;88:4398\u2013406.","journal-title":"J Clin Endocrinology & Metab"},{"key":"796_CR29","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1101\/gad.846001","volume":"15","author":"A Grapin-Botton","year":"2001","unstructured":"Grapin-Botton A, Majithia AR, Melton DA. Key events of pancreas formation are triggered in gut endoderm by ectopic expression of pancreatic regulatory genes. Genes Dev. 2001;15:444\u201354.","journal-title":"Genes Dev"},{"key":"796_CR30","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.1242\/dev.105775","volume":"141","author":"R Annunziata","year":"2014","unstructured":"Annunziata R, Arnone MI. A dynamic regulatory network explains ParaHox gene control of gut patterning in the sea urchin. Development. 2014;141:2462\u201372.","journal-title":"Development"},{"key":"796_CR31","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.molmet.2018.01.011","volume":"9","author":"X Wang","year":"2018","unstructured":"Wang X, et al. Genome-wide analysis of PDX1 target genes in human pancreatic progenitors. Molecular Metab. 2018;9:57\u201368.","journal-title":"Molecular Metab"},{"key":"796_CR32","doi-asserted-by":"publisher","first-page":"7318","DOI":"10.1073\/pnas.96.13.7318","volume":"96","author":"F Beck","year":"1999","unstructured":"Beck F, Chawengsaksophak K, Waring P, Playford RJ, Furness JB. Reprogramming of intestinal differentiation and intercalary regeneration in Cdx2 mutant mice. Proc Natl Acad Sci U S A. 1999;96:7318\u201323.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"796_CR33","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1242\/dev.125.13.2433","volume":"125","author":"LH Wu","year":"1998","unstructured":"Wu LH, Lengyel JA. Role of caudal in hindgut specification and gastrulation suggests homology between Drosophila amnioproctodeal invagination and vertebrate blastopore. Development. 1998;125:2433\u201342.","journal-title":"Development"},{"key":"796_CR34","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1006\/dbio.2000.9977","volume":"229","author":"LG Edgar","year":"2001","unstructured":"Edgar LG, Carr S, Wang H, Wood WB. Zygotic expression of the caudal homolog pal-1 is required for posterior patterning in Caenorhabditis elegans embryogenesis. Devel Biol. 2001;229:71\u201388.","journal-title":"Devel Biol"},{"key":"796_CR35","doi-asserted-by":"publisher","first-page":"7641","DOI":"10.1073\/pnas.0401654101","volume":"101","author":"K Chawengsaksophak","year":"2004","unstructured":"Chawengsaksophak K, de Graaff W, Rossant J, Deschamps J, Beck F. Cdx2 is essential for axial elongation in mouse development. Proc Natl Acad Sci U S A. 2004;101:7641\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"796_CR36","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.ydbio.2004.12.007","volume":"279","author":"T Shimizu","year":"2005","unstructured":"Shimizu T, Bae YK, Muraoka O, Hibi M. Interaction of Wnt and caudal-related genes in zebrafish posterior body formation. Devel Biol. 2005;279:125\u201341.","journal-title":"Devel Biol"},{"key":"796_CR37","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1002\/dvdy.21901","volume":"238","author":"I Faas","year":"2009","unstructured":"Faas I, Isaacs HV. Overlapping functions of Cdx1, Cdx2, and Cdx4 in the development of the amphibian Xenopus tropicalis. Devel Dynamics. 2009;238:835\u201352.","journal-title":"Devel Dynamics"},{"key":"796_CR38","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1006\/dbio.1999.9403","volume":"213","author":"Y Katsuyama","year":"1999","unstructured":"Katsuyama Y, Sato Y, Wada S, Saiga H. Ascidian tail formation requires caudal function. Devel Biol. 1999;213:257\u201368.","journal-title":"Devel Biol"},{"key":"796_CR39","doi-asserted-by":"publisher","first-page":"17711","DOI":"10.1073\/pnas.0407327102","volume":"101","author":"T Copf","year":"2004","unstructured":"Copf T, Schr\u00f6der R, Averof M. Ancestral role of caudal genes in axis elongation and segmentation. Proc Natl Acad Sci U S A. 2004;101:17711\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"796_CR40","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.mod.2004.10.001","volume":"122","author":"Y Shinmyo","year":"2005","unstructured":"Shinmyo Y, Mito T, Matsushita T, Sarashina I, Miyawaki K, Ohuchi H, Noji S. caudal is required for gnathal and thoracic patterning and for posterior elongation in the intermediate-germband cricket Gryllus bimaculatus. Mech Devel. 2005;122:231\u20139.","journal-title":"Mech Devel"},{"key":"796_CR41","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1242\/dev.125.22.4349","volume":"125","author":"J Charit\u00e9","year":"1998","unstructured":"Charit\u00e9 J, de Graaff W, Consten D, Reijnen MJ, Korving J, Deschamps J. Transducing positional information to the Hox genes: critical interaction of cdx gene products with position-sensitive regulatory elements. Development. 1998;125:4349\u201358.","journal-title":"Development"},{"key":"796_CR42","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/0092-8674(95)90104-3","volume":"83","author":"V Subramanian","year":"1995","unstructured":"Subramanian V, Meyer BI, Gruss P. Disruption of the murine homeobox gene Cdx1 affects axial skeletal identities by altering the mesodermal expression domains of Hox genes. Cell. 1995;83:641\u201353.","journal-title":"Cell"},{"key":"796_CR43","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.1093\/emboj\/17.12.3413","volume":"17","author":"HV Isaacs","year":"1998","unstructured":"Isaacs HV, Pownall ME, Slack JM. Regulation of Hox gene expression and posterior development by the Xenopus caudal homologue Xcad3. EMBO J. 1998;17:3413\u201327.","journal-title":"EMBO J"},{"key":"796_CR44","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1038\/23709","volume":"400","author":"E Moreno","year":"1999","unstructured":"Moreno E, Morata G. Caudal is the Hox gene that specifies the most posterior Drosophila segment. Nature. 1999;400:873\u20137.","journal-title":"Nature"},{"key":"796_CR45","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1242\/dev.126.4.805","volume":"126","author":"CP Hunter","year":"1999","unstructured":"Hunter CP, Harris JM, Maloof JN, Kenyon C. Hox gene expression in a single Caenorhabditis elegans cell is regulated by a caudal homolog and intercellular signals that inhibit wnt signaling. Development. 1999;126:805\u201314.","journal-title":"Development"},{"key":"796_CR46","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s00427-006-0119-y","volume":"217","author":"MA Kulakova","year":"2007","unstructured":"Kulakova MA, Bakalenko N, Novikova E, Cook CE, Eliseeva E, Steinmetz PRH, Kostyuchenko RP, Dondua A, Arendt D, Akam M, Andreeva T. Hox gene expression in the larval development of the polychaetes Nereis virens and Platynereis dumerilii (Annelida, Lophotrochozoa). Dev Genes Evol. 2007;217:39\u201354.","journal-title":"Dev Genes Evol"},{"key":"796_CR47","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13227-015-0037-z","volume":"6","author":"T Wollesen","year":"2015","unstructured":"Wollesen T, Monje SV, McDougall C, Degnan BM, Wanninger A. The ParaHox gene Gsx patterns the apical organ and central nervous system but not the foregut in scaphopod and cephalopod mollusks. Evodevo. 2015;6:41.","journal-title":"Evodevo."},{"key":"796_CR48","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.jgg.2014.02.003","volume":"41","author":"G Li","year":"2014","unstructured":"Li G, Feng J, Lei Y, Wang J, Wang H, Shang L-K, Liu D, Zhao H, Zhu Y, Wang Y. Mutagenesis at specific genomic loci of amphioxus Branchiostoma belcheri using TALEN method. J Genet Genomics. 2014;41:215\u20139.","journal-title":"J Genet Genomics"},{"issue":"14","key":"796_CR49","doi-asserted-by":"publisher","first-page":"3684","DOI":"10.1073\/pnas.1620519114","volume":"14","author":"G Li","year":"2017","unstructured":"Li G, Liu X, Xing C, Zhang H, Shimeld SM, Wang Y. Cerberus-Nodal-Lefty-Pitx signaling cascade controls left-right asymmetry in amphioxus. PNAS. 2017;14(14):3684\u20139.","journal-title":"PNAS"},{"key":"796_CR50","first-page":"81","volume":"36","author":"PR Flood","year":"1975","unstructured":"Flood PR. Fine structure of the notochord of amphioxus. Symp Zoolog Soc Lond. 1975;36:81\u2013104.","journal-title":"Symp Zoolog Soc Lond"},{"key":"796_CR51","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1111\/j.1525-142X.2011.00501.x","volume":"13","author":"D Koop","year":"2011","unstructured":"Koop D, Holland LZ, Setiamarga D, Schubert M, Holland ND. Tail regression induced by elevated retinoic acid signaling in amphioxus larvae occurs by tissue remodeling, not cell death. Evolution Devel. 2011;13:427\u201335.","journal-title":"Evolution Devel"},{"key":"796_CR52","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1111\/azo.12058","volume":"96","author":"JH Mansfield","year":"2015","unstructured":"Mansfield JH, Holland ND. Amphioxus tails: source and fate of larval fin rays and the metamorphic transition from an ectodermal to a predominantly mesodermal tail. Acta Zool. 2015;96:117\u201325.","journal-title":"Acta Zool"},{"key":"796_CR53","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s12862-016-0863-1","volume":"17","author":"JE Carvalho","year":"2017","unstructured":"Carvalho JE, Theodosiou M, Chen J, Chevret P, Alvarez S, De Lera AR, Laudet V, Croce JC, Schubert M. Lineage-specific duplication of amphioxus retinoic acid degrading enzymes (CYP26) resulted in sub-functionalization of patterning and homeostatic roles. BMC Evol Biol. 2017;17:24.","journal-title":"BMC Evol Biol"},{"key":"796_CR54","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1517\/17425250903032681","volume":"5","author":"JE Thatcher","year":"2009","unstructured":"Thatcher JE, Isoherranen N. The role of CYP26 enzymes in retinoic acid clearance. Expert Opinion on Drug Metab Tox. 2009;5:875\u201386.","journal-title":"Expert Opinion on Drug Metab Tox"},{"key":"796_CR55","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/j.1525-142X.2006.00113.x","volume":"8","author":"C Ca\u00f1estro","year":"2006","unstructured":"Ca\u00f1estro C, Postlethwait JH, Gonz\u00e0lez-Duarte R, Albalat R. Is retinoic acid genetic machinery a chordate innovation? Evolution Development. 2006;8:394\u2013406.","journal-title":"Evolution Development"},{"key":"796_CR56","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1093\/gbe\/evr084","volume":"3","author":"R Albalat","year":"2011","unstructured":"Albalat R, Brunet F, Laudet V, Schubert M. Evolution of retinoid and steroid signaling: vertebrate diversification from an amphioxus perspective. Genome Biol Evol. 2011;3:985\u20131005.","journal-title":"Genome Biol Evol"},{"key":"796_CR57","doi-asserted-by":"publisher","first-page":"4099","DOI":"10.1242\/dev.041582","volume":"136","author":"JG Savory","year":"2005","unstructured":"Savory JG, Bouchard N, Pierre V, Rijli FM, De Repentigny Y, Kothary R, Lohnes D. Cdx2 regulation of posterior development through non-Hox targets. Development. 2005;136:4099\u2013110.","journal-title":"Development"},{"key":"796_CR58","doi-asserted-by":"publisher","first-page":"3165","DOI":"10.1016\/j.celrep.2016.11.069","volume":"17","author":"S Amin","year":"2016","unstructured":"Amin S, Neijts R, Simmini S, van Rooijen C, Tan SC, Kester L, van Oudenaarden A, Creyghton MP, Deschamps J. Cdx and T Brachyury co-activate growth signaling in the embryonic axial progenitor niche. Cell Rep. 2016;17:3165\u201377.","journal-title":"Cell Rep"},{"key":"796_CR59","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.mod.2004.02.008","volume":"121","author":"B Dobbs-McAuliffe","year":"2004","unstructured":"Dobbs-McAuliffe B, Zhao Q, Linney E. Feedback mechanisms regulate retinoic acid production and degradation in the zebrafish embryo. Mech Devel. 2004;121:339\u201350.","journal-title":"Mech Devel"},{"key":"796_CR60","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.ydbio.2004.11.023","volume":"278","author":"Y Emoto","year":"2005","unstructured":"Emoto Y, Wada H, Okamoto H, Kudo A, Imai Y. Retinoic acid-metabolizing enzyme Cyp26a1 is essential for determining territories of hindbrain and spinal cord in zebrafish. Devel Biology. 2005;278:415\u201327.","journal-title":"Devel Biology"},{"key":"796_CR61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003689","volume":"9","author":"E D'Aniello","year":"2013","unstructured":"D'Aniello E, Rydeen AB, Anderson JL, Mandal A, Waxman JS. Depletion of retinoic acid receptors initiates a novel positive feedback mechanism that promotes teratogenic increases in retinoic acid. PLoS Genet. 2013;9:e1003689.","journal-title":"PLoS Genet"},{"key":"796_CR62","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/1471-2148-9-77","volume":"9","author":"EK Bomati","year":"2009","unstructured":"Bomati EK, Manning G, Deheyn DD. Amphioxus encodes the largest known family of green fluorescent proteins, which have diversified into distinct functional classes. BMC Evol Biol. 2009;9:77.","journal-title":"BMC Evol Biol"},{"key":"796_CR63","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.gene.2009.07.003","volume":"446","author":"G Li","year":"2009","unstructured":"Li G, Zhang QJ, Zhong J, Wang YQ. Evolutionary and functional diversity of green fluorescent proteins in cephalochordates. Gene. 2009;446:41\u20139.","journal-title":"Gene"},{"key":"796_CR64","first-page":"857","volume":"10","author":"M Pashmforoush","year":"1996","unstructured":"Pashmforoush M, Chan SJ, Steiner DF. Structure and expression of the insulin-like peptide receptor from amphioxus. Molec Endocrinology. 1996;10:857\u201366.","journal-title":"Molec Endocrinology"},{"key":"796_CR65","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1101\/gr.073676.107","volume":"18","author":"LZ Holland","year":"2008","unstructured":"Holland LZ, et al. The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome Res. 2008;18:1100\u201311.","journal-title":"Genome Res"},{"key":"796_CR66","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/j.0001-7272.2004.00161.x","volume":"85","author":"WR Jackman","year":"2004","unstructured":"Jackman WR, Mougey JM, Panopoulou GD, Kimmel CB. crabp and maf highlight the novelty of the amphioxus club-shaped gland. Acta Zool. 2004;85:91\u20139.","journal-title":"Acta Zool"},{"key":"796_CR67","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1242\/dev.122.12.3881","volume":"122","author":"ME Pownall","year":"1996","unstructured":"Pownall ME, Tucker AS, Slack JM, Isaacs HV. eFGF, Xcad3 and Hox genes form a molecular pathway that establishes the anteroposterior axis in Xenopus. Development. 1996;122:3881\u201392.","journal-title":"Development"},{"key":"796_CR68","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.devcel.2009.08.010","volume":"17","author":"T Young","year":"2009","unstructured":"Young T, Rowland JE, van de Ven C, Bialecka M, Novoa A, Carapuco M, van Nes J, de Graaff W, Duluc I, Freund JN, Beck F. Cdx and Hox genes differentially regulate posterior axial growth in mammalian embryos. Dev Cell. 2009;17:516\u201326.","journal-title":"Dev Cell"},{"key":"796_CR69","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41586-018-0734-6","volume":"564","author":"F Marl\u00e9taz","year":"2018","unstructured":"Marl\u00e9taz F, et al. Amphioxus functional genomics and the origins of vertebrate gene regulation. Nature. 2018;564:64\u201370.","journal-title":"Nature"},{"key":"796_CR70","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1006\/dbio.1999.9369","volume":"213","author":"H Wada","year":"1999","unstructured":"Wada H, Garcia-Fern\u00e0ndez J, Holland PWH. Colinear and segmental expression of amphioxus Hox genes. Devel Biology. 1999;213:131\u201341.","journal-title":"Devel Biology"},{"key":"796_CR71","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.ydbio.2006.04.457","volume":"296","author":"M Schubert","year":"2006","unstructured":"Schubert M, Holland ND, Laudet V, Holland LZ. A retinoic acid-Hox hierarchy controls both anterior\/posterior patterning and neuronal specification in the developing central nervous system of the cephalochordate amphioxus. Devel Biol. 2006;296:190\u2013202.","journal-title":"Devel Biol"},{"key":"796_CR72","first-page":"247","volume-title":"Advances in Comparative Endocrinology, Proceedings of the 13th International Congress on Comparative Endocrinology","author":"PWH Holland","year":"1997","unstructured":"Holland PWH, Patton SJ, Brooke NM, Garcia-Fernandez J. Genetic patterning of the ectoderm and endoderm in amphioxus: from homeobox genes to hormones. In: Kawashima S, Kikuyama S, editors. Advances in Comparative Endocrinology, Proceedings of the 13th International Congress on Comparative Endocrinology; 1997. p. 247\u201352."},{"key":"796_CR73","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119461","volume":"10","author":"C Lecroisey","year":"2015","unstructured":"Lecroisey C, Le P\u00e9tillon Y, Escriva H, Lammert E, Laudet V. Identification, evolution and expression of an insulin-like peptide in the cephalochordate Branchiostoma lanceolatum. PLoS One. 2015;10:e0119461.","journal-title":"PLoS One"},{"key":"796_CR74","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1006\/scdb.2000.0171","volume":"11","author":"K Ohneda","year":"2000","unstructured":"Ohneda K, Ee H, German M. Regulation of insulin gene transcription. Semin Cell Devel Biol. 2000;11:227\u201333.","journal-title":"Semin Cell Devel Biol"},{"key":"796_CR75","doi-asserted-by":"publisher","first-page":"95","DOI":"10.2307\/25066625","volume":"213","author":"DD Deheyn","year":"2007","unstructured":"Deheyn DD, Kubokawa K, McCarthy JK, Murakami A, Porrachia M, Rouse GW, Holland ND. Endogenous green fluorescent protein (GFP) in amphioxus. Biol Bull. 2007;213:95\u2013100.","journal-title":"Biol Bull"},{"key":"796_CR76","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1006\/bulm.2002.0319","volume":"65","author":"H Jockusch","year":"2003","unstructured":"Jockusch H, Dress A. From sphere to torus: a topological view of the metazoan body plan. Bull Math Biol. 2003;65:57\u201365.","journal-title":"Bull Math Biol"},{"key":"796_CR77","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1016\/j.cub.2005.04.063","volume":"15","author":"M Koyanagi","year":"2005","unstructured":"Koyanagi M, Kubokawa K, Tsukamoto H, Shichida Y, Terakita A. Cephalochordate melanopsin: evolutionary linkage between invertebrate visual cells and vertebrate photosensitive retinal ganglion cells. Curr Biol. 2005;15:1065\u20139.","journal-title":"Curr Biol"},{"key":"796_CR78","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1387\/ijdb.170139zk","volume":"61","author":"CN Pantzartzi","year":"2017","unstructured":"Pantzartzi CN, Pergner J, Kozmikova I, Kozmik Z. The opsin repertoire of the European lancelet: a window into light detection in a basal chordate. Int J Devel Biology. 2017;61:763\u201372.","journal-title":"Int J Devel Biology"},{"key":"796_CR79","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/S0012-1606(02)00137-9","volume":"256","author":"KD Economides","year":"2003","unstructured":"Economides KD, Zeltser L, Capecchi MR. Hoxb13 mutations cause overgrowth of caudal spinal cord and tail vertebrae. Devel Biol. 2003;256:317\u201330.","journal-title":"Devel Biol"},{"key":"796_CR80","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.devcel.2018.12.004","volume":"48","author":"R Aires","year":"2019","unstructured":"Aires R, de Lemos L, N\u00f3voa A, Jurberg AD, Mascrez B, Duboule D, Mallo M. Tail bud progenitor activity relies on a network comprising Gdf11, Lin28, and Hox13 genes. Dev Cell. 2019;48:383\u201395.","journal-title":"Dev Cell"},{"key":"796_CR81","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1101\/gad.5.2.175","volume":"5","author":"A Ruiz i Altaba","year":"1991","unstructured":"Ruiz i Altaba A, Jessell T. Retinoic acid modifies mesodermal patterning in early Xenopus embryos. Genes Dev. 1991;5:175\u201387.","journal-title":"Genes Dev"},{"key":"796_CR82","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/0887-2333(95)00012-W","volume":"9","author":"K Herrmann","year":"1995","unstructured":"Herrmann K. Teratogenic effects of retinoic acid and related substances on the early development of the zebrafish (Brachydanio rerio) as assessed by a novel scoring system. Toxicol in Vitro. 1995;9:267\u201383.","journal-title":"Toxicol in Vitro"},{"key":"796_CR83","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/S0890-6238(97)00153-6","volume":"12","author":"R Padmanabhan","year":"1998","unstructured":"Padmanabhan R. Retinoic acid-induced caudal regression syndrome in the mouse fetus. Reprod Toxicol. 1998;12:139\u201351.","journal-title":"Reprod Toxicol"},{"key":"796_CR84","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136587","volume":"10","author":"S Bertrand","year":"1991","unstructured":"Bertrand S, Aldea D, Oulion S, Subirana L, De Lera AR, Somorjai I, Escriva H. Evolution of the role of RA and FGF signals in the control of somitogenesis in chordates. PLoS One. 1991;10:e0136587.","journal-title":"PLoS One"},{"key":"796_CR85","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050838","volume":"7","author":"G Li","year":"2012","unstructured":"Li G, Yang X, Shu Z, Chen X, Wang Y. Consecutive spawnings of Chinese amphioxus, Branchiostoma belcheri, in captivity. PLoS One. 2012;7:e50838.","journal-title":"PLoS One"},{"key":"796_CR86","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075461","volume":"8","author":"G Li","year":"2013","unstructured":"Li G, Shu Z, Wang Y. Year-round reproduction and induced spawning of Chinese amphioxus, Branchiostoma belcheri, in laboratory. PLoS One. 2013;8:e75461.","journal-title":"PLoS One"},{"key":"796_CR87","doi-asserted-by":"crossref","unstructured":"Liu X, Li G, Feng J, Yang X, Wang YQ. An efficient microinjection method for unfertilized eggs of Asian amphioxus Branchiostoma belcheri. Dev Genes Evol. 2013;223(4):269\u201378.","DOI":"10.1007\/s00427-013-0441-0"},{"key":"796_CR88","doi-asserted-by":"crossref","unstructured":"Yu JK, Holland LZ. Amphioxus whole-mount in situ hybridization. Cold Spring Harb Protoc. 2009;4:1\u20136.","DOI":"10.1101\/pdb.prot5286"},{"key":"796_CR89","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1679\/aohc.51.53","volume":"51","author":"T Inou\u00e9","year":"1988","unstructured":"Inou\u00e9 T, Osatake H. A new drying method of biological specimens for scanning electron microscopy: the t-butyl alcohol freeze-drying method. Arch Histol Cytol. 1988;51:53\u20139.","journal-title":"Arch Histol Cytol"},{"key":"796_CR90","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15\u201321.","journal-title":"Bioinformatics"},{"key":"796_CR91","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s13059-017-1284-1","volume":"18","author":"NM Davidson","year":"2017","unstructured":"Davidson NM, Hawkins AD, Oshlack A. SuperTranscripts: a data driven reference for analysis and visualisation of transcriptomes. Genome Biol. 2017;18:148.","journal-title":"Genome Biol"},{"key":"796_CR92","unstructured":"Ji ZL, Li G, Qin YM. IncDNA-BF: Integrative cDNA library for Branchiostoma floridae. http:\/\/139.129.29.118\/IncDNA\/. Accessed 5 Jan 2019."},{"key":"796_CR93","doi-asserted-by":"publisher","unstructured":"Holland PWH, Li G, Herrera-\u00dabeda C. Amphioxus (Branchiostoma floridae) superTranscriptome: modified transcriptome from IncDNA-BF. 2020. University of Oxford [doi: https:\/\/doi.org\/10.5287\/bodleian:Koj7zmB7j].","DOI":"10.5287\/bodleian:Koj7zmB7j"},{"key":"796_CR94","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2013","unstructured":"Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2013;30:923\u201330.","journal-title":"Bioinformatics"},{"key":"796_CR95","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.","journal-title":"Genome Biol"},{"key":"796_CR96","unstructured":"Zhong Y, Herrera-\u00dabeda C, Garcia-Fern\u00e0ndez J, Li G, Holland PWH. RNA-seq of Branchiostoma floridae Pdx and Cdx mutants. 2020. NCBI BioProject PRJNA594548. [https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA594548]."}],"container-title":["BMC Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12915-020-00796-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12915-020-00796-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12915-020-00796-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T23:12:49Z","timestamp":1623798769000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbiol.biomedcentral.com\/articles\/10.1186\/s12915-020-00796-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,16]]},"references-count":96,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["796"],"URL":"https:\/\/doi.org\/10.1186\/s12915-020-00796-2","relation":{},"ISSN":["1741-7007"],"issn-type":[{"value":"1741-7007","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,16]]},"assertion":[{"value":"8 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"68"}}