{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:59:48Z","timestamp":1791388788319,"version":"4.3.3"},"reference-count":67,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["2013-ADG-339379"],"award-info":[{"award-number":["2013-ADG-339379"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["10-INBS-09"],"award-info":[{"award-number":["10-INBS-09"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The choroid plexus is an important blood barrier that secretes cerebrospinal fluid, which essential for embryonic brain development and adult brain homeostasis. The OTX2 homeoprotein is a transcription factor that is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative functional roles for OTX2 in adult choroid plexus function, including cell signaling and adhesion, and show that OTX2 regulates the expression of factors that are secreted into the cerebrospinal fluid, notably transthyretin. We also show that Otx2 expression impacts choroid plexus immune and stress responses, and affects splicing, leading to changes in the mRNA isoforms of proteins that are implicated in the oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell-autonomous target regions, such as the visual cortex and subventricular zone, we identify putative targets that are involved in cell adhesion, chromatin structure, and RNA processing. Thus, OTX2 retains important roles for regulating choroid plexus function and brain homeostasis throughout life.<\/jats:p>","DOI":"10.3390\/ijms22168951","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T08:44:45Z","timestamp":1629449085000},"page":"8951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["OTX2 Homeoprotein Functions in Adult Choroid Plexus"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7580-3583","authenticated-orcid":false,"given":"Anabelle","family":"Planques","sequence":"first","affiliation":[{"name":"Centre for Interdisciplinary Research in Biology (CIRB), Coll\u00e8ge de France, CNRS UMR7241, INSERM U1050, Labex MemoLife, PSL University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1859-0315","authenticated-orcid":false,"given":"Vanessa","family":"Oliveira Moreira","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Biology (CIRB), Coll\u00e8ge de France, CNRS UMR7241, INSERM U1050, Labex MemoLife, PSL University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Benacom","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Biology (CIRB), Coll\u00e8ge de France, CNRS UMR7241, INSERM U1050, Labex MemoLife, PSL University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5305-7738","authenticated-orcid":false,"given":"Cl\u00e9mence","family":"Bernard","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Biology (CIRB), Coll\u00e8ge de France, CNRS UMR7241, INSERM U1050, Labex MemoLife, PSL University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4253-1048","authenticated-orcid":false,"given":"Laurent","family":"Jourdren","sequence":"additional","affiliation":[{"name":"Genomics Core Facility, Institut de Biologie de l\u2019ENS (IBENS), D\u00e9partement de Biologie, \u00c9cole Normale Sup\u00e9rieure, CNRS, INSERM, PSL University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5820-8785","authenticated-orcid":false,"given":"Corinne","family":"Blugeon","sequence":"additional","affiliation":[{"name":"Genomics Core Facility, Institut de Biologie de l\u2019ENS (IBENS), D\u00e9partement de Biologie, \u00c9cole Normale Sup\u00e9rieure, CNRS, INSERM, PSL University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Dingli","sequence":"additional","affiliation":[{"name":"Laboratoire de Spectrom\u00e9trie de Masse Prot\u00e9omique, Centre de Recherche, Institut Curie, CEDEX 05, 75248 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5291-5646","authenticated-orcid":false,"given":"Vanessa","family":"Masson","sequence":"additional","affiliation":[{"name":"Laboratoire de Spectrom\u00e9trie de Masse Prot\u00e9omique, Centre de Recherche, Institut Curie, CEDEX 05, 75248 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9111-8842","authenticated-orcid":false,"given":"Damarys","family":"Loew","sequence":"additional","affiliation":[{"name":"Laboratoire de Spectrom\u00e9trie de Masse Prot\u00e9omique, Centre de Recherche, Institut Curie, CEDEX 05, 75248 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7626-5863","authenticated-orcid":false,"given":"Alain","family":"Prochiantz","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Biology (CIRB), Coll\u00e8ge de France, CNRS UMR7241, INSERM U1050, Labex MemoLife, PSL University, 75005 Paris, France"},{"name":"Institute of Neurosciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel A.","family":"Di Nardo","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Biology (CIRB), Coll\u00e8ge de France, CNRS UMR7241, INSERM U1050, Labex MemoLife, PSL University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.devcel.2020.01.027","article-title":"Emergence and Developmental Roles of the Cerebrospinal Fluid System","volume":"52","author":"Fame","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1242\/dev.090860","article-title":"The transcription factor Otx2 regulates choroid plexus development and function","volume":"140","author":"Johansson","year":"2013","journal-title":"Development"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4903","DOI":"10.1523\/JNEUROSCI.3081-14.2015","article-title":"Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production","volume":"35","author":"Lun","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","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":"ref_5","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1016\/j.celrep.2013.05.014","article-title":"Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity","volume":"3","author":"Spatazza","year":"2013","journal-title":"Cell Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/dvdy.24060","article-title":"Non-transcriptional interactions of Hox proteins: Inventory, facts, and future directions","volume":"243","author":"Rezsohazy","year":"2014","journal-title":"Dev. Dyn."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1152\/physrev.00018.2017","article-title":"The physiology of homeoprotein transduction","volume":"98","author":"Fuchs","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"eabc6374","DOI":"10.1126\/sciadv.abc6374","article-title":"Homeoprotein transduction in neurodevelopment and physiopathology","volume":"6","author":"Joliot","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.celrep.2015.06.043","article-title":"OTX2 Transcription Factor Controls Regional Patterning within the Medial Ganglionic Eminence and Regional Identity of the Septum","volume":"12","author":"Hoch","year":"2015","journal-title":"Cell Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12567","DOI":"10.1111\/jpi.12567","article-title":"Homeobox genes in melatonin-producing pinealocytes: Otx2 and Crx act to promote hormone synthesis in the mature rat pineal gland","volume":"66","author":"Rohde","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/s41586-018-0581-5","article-title":"OTX2 restricts entry to the mouse germline","volume":"562","author":"Zhang","year":"2018","journal-title":"Nature"},{"key":"ref_12","first-page":"1948","article-title":"ChIP-seq analysis of genomic binding regions of five major transcription factors in mouse epiblast stem cells that highlights a central role for ZIC2","volume":"144","author":"Matsuda","year":"2017","journal-title":"Development"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1016\/j.celrep.2016.05.041","article-title":"Loss of the Otx2-Binding Site in the Nanog Promoter Affects the Integrity of Embryonic Stem Cell Subtypes and Specification of Inner Cell Mass-Derived Epiblast","volume":"15","author":"Acampora","year":"2016","journal-title":"Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Samuel, A., Housset, M., Fant, B., and Lamonerie, T. (2014). Otx2 ChIP-seq reveals unique and redundant functions in the mature mouse retina. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089110"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/dvg.22903","article-title":"Comprehensive interactome of Otx2 in the adult mouse neural retina","volume":"53","author":"Fant","year":"2015","journal-title":"Genesis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1093\/cercor\/bhy108","article-title":"Non-cell Autonomous OTX2 Homeoprotein Regulates Visual Cortex Plasticity Through Gadd45b\/g","volume":"29","author":"Apulei","year":"2019","journal-title":"Cereb. Cortex"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3389\/fnins.2017.00307","article-title":"Genome-wide target analyses of Otx2 homeoprotein in postnatal cortex","volume":"11","author":"Sakai","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1126\/science.aan4491","article-title":"Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2","volume":"356","author":"Kronman","year":"2017","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Planques, A., Oliveira Moreira, V., Dubreuil, C., Prochiantz, A., and Di Nardo, A.A. (2019). OTX2 Signals from the Choroid Plexus to Regulate Adult Neurogenesis. eNeuro, 6.","DOI":"10.1101\/243659"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.cell.2008.05.054","article-title":"Experience-Dependent Transfer of Otx2 Homeoprotein into the Visual Cortex Activates Postnatal Plasticity","volume":"134","author":"Sugiyama","year":"2008","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1093\/hmg\/ddt562","article-title":"Graded Otx2 activities demonstrate dose-sensitive eye and retina phenotypes","volume":"23","author":"Bernard","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1126\/science.1252945","article-title":"Aging-induced type I interferon response at the choroid plexus negatively affects brain function","volume":"346","author":"Baruch","year":"2014","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.stem.2016.06.013","article-title":"Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult Neural Stem Cells","volume":"19","author":"Mizrak","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.neuron.2011.01.023","article-title":"The Cerebrospinal Fluid Provides a Proliferative Niche for Neural Progenitor Cells","volume":"69","author":"Lehtinen","year":"2011","journal-title":"Neuron"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.devcel.2015.01.010","article-title":"It takes a village: Constructing the neurogenic niche","volume":"32","author":"Bjornsson","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1523\/JNEUROSCI.4729-03.2004","article-title":"Multiple Roles for Slits in the Control of Cell Migration in the Rostral Migratory Stream","volume":"24","author":"Sotelo","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1126\/science.1119133","article-title":"New neurons follow the flow of cerebrospinal fluid in the adult brain","volume":"311","author":"Sawamoto","year":"2006","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/stem.1095","article-title":"IGF-II promotes stemness of neural restricted precursors","volume":"30","author":"Ziegler","year":"2012","journal-title":"Stem Cells"},{"key":"ref_29","doi-asserted-by":"crossref","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":"ref_30","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1046\/j.1474-9728.2003.00046.x","article-title":"Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice","volume":"2","author":"Jin","year":"2003","journal-title":"Aging Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/cpr.12023","article-title":"Fractone-heparan sulphates mediate FGF-2 stimulation of cell proliferation in the adult subventricular zone","volume":"46","author":"Douet","year":"2013","journal-title":"Cell Prolif."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1179\/016164101101198550","article-title":"FGF-2 immunoreactivity in adult rat ependyma and choroid plexus: Responses to global forebrain ischemia and intraventricular FGF-2","volume":"23","author":"Hayamizu","year":"2001","journal-title":"Neurol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7850","DOI":"10.1523\/JNEUROSCI.17-20-07850.1997","article-title":"Der Transforming growth factor-\u03b1 null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma","volume":"17","author":"Tropepe","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1097\/01.jnen.0000218444.53405.f0","article-title":"Transforming growth factor-\u03b21 is a negative modulator of adult neurogenesis","volume":"65","author":"Wachs","year":"2006","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1089\/hum.2005.16.49","article-title":"Transduction of the choroid plexus and ependyma in neonatal mouse brain by vesicular stomatitis virus glycoprotein-pseudotyped lentivirus and adeno-associated virus type 5 vectors","volume":"16","author":"Watson","year":"2005","journal-title":"Hum. Gene Ther."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Arnaud, K., Moreira, V.O., Vincent, J., Dallerac, G., le Poupon, C., Richter, M., M\u00fcller, U., Rondi-Reig, L., Prochiantz, A., and di Nardo, A. (2019). Choroid plexus APP regulates adult brain proliferation and animal behavior. bioRxiv.","DOI":"10.1101\/734103"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3389\/fphys.2019.00005","article-title":"The Extracellular Protein, Transthyretin Is an Oxidative Stress Biomarker","volume":"10","author":"Sharma","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4331\/wjbc.v3.i5.93","article-title":"Peroxisomes, oxidative stress, and inflammation","volume":"3","author":"Terlecky","year":"2012","journal-title":"World J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00418-013-1110-0","article-title":"Intermediate filaments are important for astrocyte response to oxidative stress induced by oxygen-glucose deprivation and reperfusion","volume":"140","author":"Nilsson","year":"2013","journal-title":"Histochem. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"178","DOI":"10.12688\/f1000research.4869.1","article-title":"Immunoprecipitation and mass spectrometry identify non-cell autonomous Otx2 homeoprotein in the granular and supragranular layers of mouse visual cortex","volume":"3","author":"Kim","year":"2014","journal-title":"F1000Research"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.molcel.2019.09.014","article-title":"Properties of Stress Granule and P-Body Proteomes","volume":"76","author":"Youn","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10815","DOI":"10.1073\/pnas.0403824101","article-title":"Emx2 homeodomain transcription factor interacts with eukaryotic translation initiation factor 4E (eIF4E) in the axons of olfactory sensory neurons","volume":"101","author":"Foucher","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.devcel.2019.11.019","article-title":"Mitotic Implantation of the Transcription Factor Prospero via Phase Separation Drives Terminal Neuronal Differentiation","volume":"52","author":"Liu","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e97374","DOI":"10.15252\/embj.201797374","article-title":"Engrailed homeoprotein blocks degeneration in adult dopaminergic neurons through LINE-1 repression","volume":"37","author":"Rekaik","year":"2018","journal-title":"EMBO J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1242\/dev.037770","article-title":"Meis2 competes with the Groucho co-repressor Tle4 for binding to Otx2 and specifies tectal fate without induction of a secondary midbrain-hindbrain boundary organizer","volume":"136","author":"Agoston","year":"2009","journal-title":"Development"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1128\/MCB.00811-06","article-title":"Gbx2 and Otx2 Interact with the WD40 Domain of Groucho\/Tle Corepressors","volume":"27","author":"Heimbucher","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/bies.201300012","article-title":"Phosphatidylinositol 3,5-bisphosphate: Low abundance, high significance","volume":"36","author":"McCartney","year":"2014","journal-title":"BioEssays"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1128\/MCB.25.3.1100-1112.2005","article-title":"Eukaryotic Translation Initiation Factor 4E Activity Is Modulated by HOXA9 at Multiple Levels","volume":"25","author":"Topisirovic","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9172","DOI":"10.1074\/jbc.M608067200","article-title":"Neural stem\/progenitor cells express 20 tenascin C isoforms that are differentially regulated by Pax6","volume":"282","author":"Egbers","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1038\/cdd.2017.140","article-title":"Fine-tuning and autoregulation of the intestinal determinant and tumor suppressor homeobox gene CDX2 by alternative splicing","volume":"24","author":"Balbinot","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1038\/sj.embor.7400751","article-title":"Temporal and spatial delineation of mouse Otx2 functions by conditional self-knockout","volume":"7","author":"Fossat","year":"2006","journal-title":"EMBO Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.mod.2009.07.003","article-title":"Selective inactivation of Otx2 mRNA isoforms reveals isoform-specific requirement for visceral endoderm anteriorization and head morphogenesis and highlights cell diversity in the visceral endoderm","volume":"126","author":"Acampora","year":"2009","journal-title":"Mech. Dev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"Fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1093\/bioinformatics\/btz247","article-title":"IsoformSwitchAnalyzeR: Analysis of changes in genome-wide patterns of alternative splicing and its functional consequences","volume":"35","author":"Sandelin","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1158\/1541-7786.MCR-16-0459","article-title":"The landscape of isoform switches in human cancers","volume":"15","author":"Sandelin","year":"2017","journal-title":"Mol. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1101\/gr.133744.111","article-title":"Detecting differential usage of exons from RNA-seq data","volume":"22","author":"Anders","year":"2012","journal-title":"Genome Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1093\/nar\/gkt006","article-title":"CPAT: Coding-potential assessment tool using an alignment-free logistic regression model","volume":"41","author":"Wang","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/prot.25674","article-title":"NetSurfP-2.0: Improved prediction of protein structural features by integrated deep learning","volume":"87","author":"Klausen","year":"2019","journal-title":"Prot. Struct. Funct. Bioinform."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41587-019-0036-z","article-title":"SignalP 5.0 improves signal peptide predictions using deep neural networks","volume":"37","author":"Tsirigos","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"D222","DOI":"10.1093\/nar\/gkt1223","article-title":"Pfam: The protein families database","volume":"42","author":"Finn","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1002\/pmic.200600784","article-title":"myProMS, a web server for management and validation of mass spectrometry-based proteomic data","volume":"7","author":"Poullet","year":"2007","journal-title":"Proteomics"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1021\/pr801109k","article-title":"Improvements to the percolator algorithm for peptide identification from shotgun proteomics data sets","volume":"8","author":"Spivak","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Vincent, C., Gilabert-Juan, J., Gibel-Russo, R., Alvarez-Fischer, D., Krebs, M.-O., Le Pen, G., Prochiantz, A., and Di Nardo, A.A. (2021). Non-cell-autonomous OTX2 transcription factor regulates anxiety-related behavior in the mouse. Mol. Psychiatry, 1\u201312.","DOI":"10.1038\/s41380-021-01132-y"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8951\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:47:33Z","timestamp":1760165253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,19]]},"references-count":67,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168951"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168951","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.04.28.441734","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,19]]}}}