{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:10:39Z","timestamp":1787026239586,"version":"build-2736575974"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    The Wilms tumor suppressor gene\n                    <jats:italic>Wt1<\/jats:italic>\n                    encodes a zinc finger transcription factor, which is highly conserved among vertebrates. It is a key regulator of urogenital development and homeostasis but also plays a role in other organs including the spleen and the heart. More recently additional functions for Wt1 in the mammalian central nervous system have been described. In contrast to mammals, bony fish possess two paralogous\n                    <jats:italic>Wt1<\/jats:italic>\n                    genes, namely\n                    <jats:italic>wt1a<\/jats:italic>\n                    and\n                    <jats:italic>wt1b.<\/jats:italic>\n                    By performing detailed\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization analyses during zebrafish development, we discovered new expression domains for\n                    <jats:italic>wt1a<\/jats:italic>\n                    in the dorsal hindbrain, the caudal medulla and the spinal cord. Marker analysis identified\n                    <jats:italic>wt1a<\/jats:italic>\n                    expressing cells of the dorsal hindbrain as ependymal cells of the choroid plexus in the myelencephalic ventricle. The choroid plexus acts as a blood-cerebrospinal fluid barrier and thus is crucial for brain homeostasis. By employing\n                    <jats:italic>wt1a<\/jats:italic>\n                    mutant larvae and a dye accumulation assay with fluorescent tracers we demonstrate that Wt1a is required for proper choroid plexus formation and function. Thus, Wt1a contributes to the barrier properties of the choroid plexus in zebrafish, revealing an unexpected role for Wt1 in the zebrafish brain.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2021.809962","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T23:39:29Z","timestamp":1641857969000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The Wilms Tumor Gene wt1a Contributes to Blood-Cerebrospinal Fluid Barrier Function in Zebrafish"],"prefix":"10.3389","volume":"9","author":[{"given":"Vera L.","family":"Hopfenm\u00fcller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Perner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Reuter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J. D.","family":"Bates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Gro\u00dfe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Englert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"219","DOI":"10.2174\/1874609811003030219","article-title":"Clearance of Amyloid-\u03b2 Peptide across the Choroid Plexus in Alzheimers Disease","volume":"3","author":"Alvira-Botero","year":"2010","journal-title":"Curr. Aging Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/0925-4773(93)90090-k","article-title":"The Expression of the Wilms' Tumour Gene, WT1, in the Developing Mammalian Embryo","volume":"40","author":"Armstrong","year":"1993","journal-title":"Mech. Dev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/ng1228","article-title":"Cryptic Boundaries in Roof Plate and Choroid Plexus Identified by Intersectional Gene Activation","volume":"35","author":"Awatramani","year":"2003","journal-title":"Nat. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e3114","DOI":"10.1371\/journal.pone.0003114","article-title":"Development and Notch Signaling Requirements of the Zebrafish Choroid Plexus","volume":"3","author":"Bill","year":"2008","journal-title":"PLoS One"},{"key":"B5","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1002\/dvdy.20645","article-title":"Identification and Comparative Expression Analysis of a Secondwt1 Gene in Zebrafish","volume":"235","author":"Bollig","year":"2006","journal-title":"Dev. Dyn."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2883","DOI":"10.1242\/dev.031773","article-title":"A Highly Conserved Retinoic Acid Responsive Element Controls Wt1a Expression in the Zebrafish Pronephros","volume":"136","author":"Bollig","year":"2009","journal-title":"Development"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e1002404","DOI":"10.1371\/journal.pgen.1002404","article-title":"Acute Multiple Organ Failure in Adult Mice Deleted for the Developmental Regulator Wt1","volume":"7","author":"Chau","year":"2011","journal-title":"Plos Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"304","DOI":"10.3389\/fphys.2013.00304","article-title":"Na+ Dependent Acid-Base Transporters in the Choroid Plexus; Insights from Slc4 and Slc9 Gene Deletion Studies","volume":"4","author":"Christensen","year":"2013","journal-title":"Front. Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3549","DOI":"10.1242\/dev.01915","article-title":"Direct and Indirect Roles of CNS Dorsal Midline Cells in Choroid Plexus Epithelia Formation","volume":"132","author":"Currle","year":"2005","journal-title":"Development"},{"key":"B10","doi-asserted-by":"publisher","first-page":"3056","DOI":"10.1016\/j.cell.2021.04.003","article-title":"A Cellular and Spatial Map of the Choroid Plexus across Brain Ventricles and Ages","volume":"184","author":"Dani","year":"2021","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s00401-009-0624-y","article-title":"Ependymal Cells: Biology and Pathology","volume":"119","author":"Del Bigio","year":"2010","journal-title":"Acta Neuropathol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"0047","DOI":"10.1523\/ENEURO.0047-20.2020","article-title":"Behavioral Characterization of Dmrt3a Mutant Zebrafish Reveals Crucial Aspects of Vertebrate Locomotion through Phenotypes Related to Acceleration","volume":"7","author":"Del Pozo","year":"2020","journal-title":"eNeuro"},{"key":"B13","doi-asserted-by":"publisher","first-page":"109775","DOI":"10.1016\/j.celrep.2021.109775","article-title":"Diversity and Function of Motile Ciliated Cell Types within Ependymal Lineages of the Zebrafish Brain","volume":"37","author":"D\u2019Gama","year":"2021","journal-title":"Cel Rep."},{"key":"B14","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1038\/ki.2015.198","article-title":"Towards an Understanding of Kidney Diseases Associated with WT1 Mutations","volume":"88","author":"Dong","year":"","journal-title":"Kidney Int."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2118","DOI":"10.1681\/ASN.2014080819","article-title":"Integration of Cistromic and Transcriptomic Analyses Identifies Nphs2, Mafb, and Magi2 as Wilms' Tumor 1 Target Genes in Podocyte Differentiation and Maintenance","volume":"26","author":"Dong","year":"","journal-title":"J. Am. Soc. Nephrol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1002\/jnr.10410","article-title":"Amphiregulin Is a Mitogen for Adult Neural Stem Cells","volume":"69","author":"Falk","year":"2002","journal-title":"J. Neurosci. Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e3090","DOI":"10.1371\/journal.pone.0003090","article-title":"In Vivo analysis of Choroid Plexus Morphogenesis in Zebrafish","volume":"3","author":"Garc\u00eda-Lecea","year":"2008","journal-title":"PLoS One"},{"key":"B18","doi-asserted-by":"publisher","first-page":"5666","DOI":"10.1523\/JNEUROSCI.0328-18.2018","article-title":"WT1-Expressing Interneurons Regulate Left-Right Alternation during Mammalian Locomotor Activity","volume":"38","author":"Haque","year":"2018","journal-title":"J. Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/0168-9525(90)90008-t","article-title":"Two-color Whole-Mount In Situ Hybridization to Vertebrate and Drosophila Embryos","volume":"10","author":"Hauptmann","year":"1994","journal-title":"Trends Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"364","DOI":"10.3389\/fnins.2014.00364","article-title":"Functional and Genetic Analysis of Choroid Plexus Development in Zebrafish","volume":"8","author":"Henson","year":"2014","journal-title":"Front. Neurosci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/s0960-9822(99)80369-8","article-title":"The Wilms Tumor Suppressor Gene Wt1 Is Required for Development of the Spleen","volume":"9","author":"Herzer","year":"1999","journal-title":"Curr. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2535","DOI":"10.1242\/dev.033795","article-title":"Sonic Hedgehog Signaling Regulates a Novel Epithelial Progenitor Domain of the Hindbrain Choroid Plexus","volume":"136","author":"Huang","year":"2009","journal-title":"Development"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1242\/dev.021535","article-title":"Hes Genes and Neurogenin Regulate Non-neural versus Neural Fate Specification in the Dorsal Telencephalic Midline","volume":"135","author":"Imayoshi","year":"2008","journal-title":"Development"},{"key":"B24","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1002\/jnr.10843","article-title":"Patterns of Jagged1, Jagged2, Delta-like 1 and Delta-like 3 Expression during Late Embryonic and Postnatal Brain Development Suggest Multiple Functional Roles in Progenitors and Differentiated Cells","volume":"75","author":"Irvin","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"14585","DOI":"10.1074\/jbc.M109.094334","article-title":"A Novel Wilms Tumor 1 (WT1) Target Gene Negatively Regulates the WNT Signaling Pathway","volume":"285","author":"Kim","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of Embryonic Development of the Zebrafish","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev. Dyn."},{"key":"B27","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/0092-8674(93)90515-r","article-title":"WT-1 Is Required for Early Kidney Development","volume":"74","author":"Kreidberg","year":"1993","journal-title":"Cell"},{"key":"B28","doi-asserted-by":"publisher","first-page":"32","DOI":"10.3389\/fnins.2015.00032","article-title":"Development of the Choroid Plexus and Blood-CSF Barrier","volume":"9","author":"Liddelow","year":"2015","journal-title":"Front. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1242\/dev.01791","article-title":"Initial Formation of Zebrafish Brain Ventricles Occurs Independently of Circulation and Requires the Nagie Oko and snakehead\/atp1a1a.1 Gene Products","volume":"132","author":"Lowery","year":"2005","journal-title":"Development"},{"key":"B30","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nrn3921","article-title":"Development and Functions of the Choroid Plexus-Cerebrospinal Fluid System","volume":"16","author":"Lun","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"13759","DOI":"10.1038\/ncomms13759","article-title":"Bi- and Uniciliated Ependymal Cells Define Continuous Floor-Plate-Derived Tanycytic Territories","volume":"8","author":"Mirzadeh","year":"2017","journal-title":"Nat. Commun."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1242\/dev.126.9.1845","article-title":"YAC Complementation Shows a Requirement for Wt1 in the Development of Epicardium, Adrenal Gland and throughout Nephrogenesis","volume":"126","author":"Moore","year":"1999","journal-title":"Development"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1242\/dev.119.4.1329","article-title":"Nuclear Localization of the Protein Encoded by the Wilms' Tumor Gene WT1 in Embryonic and Adult Tissues","volume":"119","author":"Mundlos","year":"1993","journal-title":"Development"},{"key":"B34","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.ydbio.2010.01.032","article-title":"Sonic Hedgehog Is Required for Vascular Outgrowth in the Hindbrain Choroid Plexus","volume":"340","author":"Nielsen","year":"2010","journal-title":"Dev. Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1743-8454-5-16","article-title":"Hydrocephalus Caused by Conditional Ablation of the Pten or Beta-Catenin Gene","volume":"5","author":"Ohtoshi","year":"2008","journal-title":"Fluids Barriers CNS"},{"key":"B36","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1152\/physrev.00020.2002","article-title":"Cell Biology of the Glomerular Podocyte","volume":"83","author":"Pavenst\u00e4dt","year":"2003","journal-title":"Physiol. Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.ydbio.2007.06.022","article-title":"The Wilms Tumor Genes Wt1a and Wt1b Control Different Steps during Formation of the Zebrafish Pronephros","volume":"309","author":"Perner","year":"2007","journal-title":"Dev. Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A New Mathematical Model for Relative Quantification in Real-Time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1016\/j.celrep.2019.06.091","article-title":"Wilms Tumor 1b Expression Defines a Pro-regenerative Macrophage Subtype and Is Required for Organ Regeneration in the Zebrafish","volume":"28","author":"Sanz-Morej\u00f3n","year":"2019","journal-title":"Cel Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e139","DOI":"10.1038\/tp.2012.64","article-title":"A Molecular Characterization of the Choroid Plexus and Stress-Induced Gene Regulation","volume":"2","author":"Sathyanesan","year":"2012","journal-title":"Transl Psychiatry"},{"key":"B41","doi-asserted-by":"publisher","first-page":"529487","DOI":"10.3389\/fnins.2020.529487","article-title":"Wt1 Positive dB4 Neurons in the Hindbrain Are Crucial for Respiration","volume":"14","author":"Schnerwitzki","year":"2020","journal-title":"Front. Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ydbio.2014.06.026","article-title":"Alternative Splicing of Wilms Tumor Suppressor 1 (Wt1) Exon 4 Results in Protein Isoforms with Different Functions","volume":"393","author":"Schnerwitzki","year":"2014","journal-title":"Dev. Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e201800106","DOI":"10.26508\/lsa.201800106","article-title":"Neuron-specific Inactivation of Wt1 Alters Locomotion in Mice and Changes Interneuron Composition in the Spinal Cord","volume":"1","author":"Schnerwitzki","year":"2018","journal-title":"Life Sci. Alliance"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/j.cell.2018.03.063","article-title":"Single-Cell Transcriptomics and Fate Mapping of Ependymal Cells Reveals an Absence of Neural Stem Cell Function","volume":"173","author":"Shah","year":"2018","journal-title":"Cell"},{"key":"B45","first-page":"6407","article-title":"Molecular Cloning of Rat Wilms' Tumor Complementary DNA and a Study of Messenger RNA Expression in the Urogenital System and the Brain","volume":"52","author":"Sharma","year":"1992","journal-title":"Cancer Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.expneurol.2015.02.032","article-title":"A Balanced View of Choroid Plexus Structure and Function: Focus on Adult Humans","volume":"267","author":"Spector","year":"2015","journal-title":"Exp. Neurol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"5063","DOI":"10.3892\/ol.2019.10882","article-title":"Next Generation DNA Sequencing of Atypical Choroid Plexus Papilloma of Brain: Identification of Novel Mutations in a Female Patient by Ion Proton","volume":"18","author":"Taher","year":"2019","journal-title":"Oncol. Lett."},{"key":"B48","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/j.ccell.2015.04.005","article-title":"Cross-Species Genomics Identifies TAF12, NFYC, and RAD54L as Choroid Plexus Carcinoma Oncogenes","volume":"27","author":"Tong","year":"2015","journal-title":"Cancer Cell"},{"key":"B49","doi-asserted-by":"publisher","first-page":"bio030494","DOI":"10.1242\/bio.030494","article-title":"A Transgenic Zebrafish Model for the In Vivo Study of the Blood and Choroid Plexus Brain Barriers Using Claudin 5","volume":"7","author":"van Leeuwen","year":"2018","journal-title":"Biol. Open"},{"key":"B50","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.jneuroim.2008.04.035","article-title":"Involvement of the Choroid Plexus in Multiple Sclerosis Autoimmune Inflammation: a Neuropathological Study","volume":"199","author":"Vercellino","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.ydbio.2011.05.668","article-title":"WT1 Regulates Epicardial Epithelial to Mesenchymal Transition through \u03b2-catenin and Retinoic Acid Signaling Pathways","volume":"356","author":"von Gise","year":"2011","journal-title":"Dev. Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.theriogenology.2019.07.007","article-title":"Influence of Wilms' Tumor Suppressor Gene WT1 on Bovine Sertoli Cells Polarity and Tight Junctions via Non-canonical WNT Signaling Pathway","volume":"138","author":"Wang","year":"2019","journal-title":"Theriogenology"},{"key":"B53","doi-asserted-by":"publisher","first-page":"e1003645","DOI":"10.1371\/journal.pgen.1003645","article-title":"The Wilms Tumor Gene, Wt1, Is Critical for Mouse Spermatogenesis via Regulation of Sertoli Cell Polarity and Is Associated with Non-obstructive Azoospermia in Humans","volume":"9","author":"Wang","year":"2013","journal-title":"Plos Genet."},{"key":"B54","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00401-009-0627-8","article-title":"Choroid Plexus: Biology and Pathology","volume":"119","author":"Wolburg","year":"2010","journal-title":"Acta Neuropathol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.aaf.2018.04.004","article-title":"The Dysregulated Autophagy Signaling Is Partially Responsible for Defective Podocyte Development in Wt1a Mutant Zebrafish","volume":"3","author":"Zhang","year":"2018","journal-title":"Aquacult. Fish."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.809962\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T23:39:32Z","timestamp":1641857972000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.809962\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,11]]},"references-count":55,"alternative-id":["10.3389\/fcell.2021.809962"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.809962","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,11]]},"article-number":"809962"}}