{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T18:44:53Z","timestamp":1776278693024,"version":"3.50.1"},"posted":{"date-parts":[[2026,4,12]]},"group-title":"Developmental Biology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","award":["R01MH118344"],"award-info":[{"award-number":["R01MH118344"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Breakthrough Discoveries for thriving with Bipolar Disorder","award":["DG230102"],"award-info":[{"award-number":["DG230102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Bipolar disorder (BD) is a prevalent and highly heritable psychiatric condition. Developmental mechanisms are implicated but the specific molecular origins remain unclear. The choroid plexus (ChP), which regulates cerebrospinal fluid (CSF) and brain homeostasis, has been implicated in BD, but its role is poorly understood. Here, we identify aberrant expansion of ChP in human cortical (hCOs) and ChP organoids (hChPOs) derived from, and\n                  <jats:italic>in vivo<\/jats:italic>\n                  structural magnetic resonance imaging (sMRI) scans of, individuals with BD compared to healthy comparison individuals. Single-cell transcriptomics revealed a lineage bias toward ChP fate in BD hCOs, accompanied by structural enlargement observed in both BD hChPOs and ChP in sMRI scans from individuals with BD. Comprehensive transcriptomic profiling implicates early hyperactivation of the Hippo signaling pathway in neural progenitor cells as a convergent mechanism driving ChP overgrowth. Whole-genome and genome-wide association study analyses highlight recurrent genetic variants in Hippo regulators, including\n                  <jats:italic>STK4<\/jats:italic>\n                  and\n                  <jats:italic>YAP1<\/jats:italic>\n                  , suggesting genetic priming. BD hChPOs exhibit disrupted epithelial junctions and altered\n                  <jats:italic>in vitro<\/jats:italic>\n                  CSF secretion. These findings position the ChP as a genetically and developmentally predisposed to pathology in BD and highlight organoids as a platform for translational discovery in diagnostics and therapeutics.\n                <\/jats:p>","DOI":"10.64898\/2026.04.10.717745","type":"posted-content","created":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T09:35:12Z","timestamp":1775986512000},"source":"Crossref","is-referenced-by-count":0,"title":["Dysregulation of Hippo Signaling Pathway as a Convergent Mechanism Underlying Choroid Plexus Defects in Bipolar Disorder"],"prefix":"10.64898","author":[{"given":"Jonghun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT, USA"},{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Wu Tsai Institute, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mu Seog","family":"Choe","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT, USA"},{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Wu Tsai Institute, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kutlu","family":"Kaya","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA"},{"name":"BD2: Breakthrough Discoveries for Thriving with Bipolar Disorder, Santa Monica, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth K.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caihong","family":"Qiu","sequence":"additional","affiliation":[{"name":"Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo Sub","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT, USA"},{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Wu Tsai Institute, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdi Ridvan","family":"Kiral","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT, USA"},{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Wu Tsai Institute, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT, USA"},{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Wu Tsai Institute, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Scandura","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT, USA"},{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Wu Tsai Institute, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyuk-Jin","family":"Cha","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7640-2071","authenticated-orcid":false,"given":"Jeffrey R.","family":"Gruen","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT, USA"},{"name":"Departments of Pediatrics, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monkol","family":"Lek","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Jonas","sequence":"additional","affiliation":[{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"},{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA"},{"name":"Marine Biological Laboratory, Woods Hole, MA"},{"name":"Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA"},{"name":"BD2: Breakthrough Discoveries for Thriving with Bipolar Disorder, Santa Monica, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilary P.","family":"Blumberg","sequence":"additional","affiliation":[{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Wu Tsai Institute, Yale School of Medicine, New Haven, CT, USA"},{"name":"Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA"},{"name":"Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In-Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT, USA"},{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA"},{"name":"Wu Tsai Institute, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041510500846000_2026.04.10.717745v1.1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.64.5.543"},{"key":"2026041510500846000_2026.04.10.717745v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2023.115601"},{"key":"2026041510500846000_2026.04.10.717745v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-025-02887-4"},{"key":"2026041510500846000_2026.04.10.717745v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2009.39"},{"key":"2026041510500846000_2026.04.10.717745v1.5","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.56.3.254"},{"key":"2026041510500846000_2026.04.10.717745v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.227"},{"key":"2026041510500846000_2026.04.10.717745v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw181"},{"key":"2026041510500846000_2026.04.10.717745v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00857-4"},{"key":"2026041510500846000_2026.04.10.717745v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08468-9"},{"key":"2026041510500846000_2026.04.10.717745v1.10","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2019.18070825"},{"key":"2026041510500846000_2026.04.10.717745v1.11","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.13585"},{"key":"2026041510500846000_2026.04.10.717745v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2023.11.036"},{"key":"2026041510500846000_2026.04.10.717745v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2025.03.047"},{"key":"2026041510500846000_2026.04.10.717745v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2022.01.007"},{"key":"2026041510500846000_2026.04.10.717745v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01866-3"},{"key":"2026041510500846000_2026.04.10.717745v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.03.026"},{"key":"2026041510500846000_2026.04.10.717745v1.17","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12664"},{"key":"2026041510500846000_2026.04.10.717745v1.18","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz5626"},{"key":"2026041510500846000_2026.04.10.717745v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2022.100441"},{"key":"2026041510500846000_2026.04.10.717745v1.20","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028753"},{"key":"2026041510500846000_2026.04.10.717745v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2023.102797"},{"key":"2026041510500846000_2026.04.10.717745v1.22","doi-asserted-by":"publisher","DOI":"10.1021\/pr070247w"},{"key":"2026041510500846000_2026.04.10.717745v1.23","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S193616"},{"key":"2026041510500846000_2026.04.10.717745v1.24","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.8b00809"},{"key":"2026041510500846000_2026.04.10.717745v1.25","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201000371"},{"key":"2026041510500846000_2026.04.10.717745v1.26","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201100061"},{"key":"2026041510500846000_2026.04.10.717745v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2006.10.031"},{"key":"2026041510500846000_2026.04.10.717745v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.285"},{"key":"2026041510500846000_2026.04.10.717745v1.29","unstructured":"First, M. B. , Williams, J. B. , Karg, R. S. & Spitzer, R. L. Structured clinical interview for DSM-5 disorders. Clinician Version (SCID-5-CV) (2015)."},{"key":"2026041510500846000_2026.04.10.717745v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1781(95)02632-7"},{"key":"2026041510500846000_2026.04.10.717745v1.31","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.18588"},{"key":"2026041510500846000_2026.04.10.717745v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.pscychresns.2011.07.005"},{"key":"2026041510500846000_2026.04.10.717745v1.33","doi-asserted-by":"crossref","unstructured":"First, M. B. Standardized evaluation in clinical practice. 1st edn, (American Psychiatric Pub., 2003).","DOI":"10.1176\/appi.books.9781615377268"},{"key":"2026041510500846000_2026.04.10.717745v1.34","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhg087"},{"key":"2026041510500846000_2026.04.10.717745v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00569-X"},{"key":"2026041510500846000_2026.04.10.717745v1.36","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-190706"},{"key":"2026041510500846000_2026.04.10.717745v1.37","doi-asserted-by":"publisher","DOI":"10.1007\/s10462-012-9317-3"},{"key":"2026041510500846000_2026.04.10.717745v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpc.2010.04.018"},{"key":"2026041510500846000_2026.04.10.717745v1.39","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007963824710"},{"key":"2026041510500846000_2026.04.10.717745v1.40","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.984929"},{"key":"2026041510500846000_2026.04.10.717745v1.41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004219"},{"key":"2026041510500846000_2026.04.10.717745v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01261-5"},{"key":"2026041510500846000_2026.04.10.717745v1.43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-985X.2010.00676_9.x"},{"key":"2026041510500846000_2026.04.10.717745v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3192"},{"key":"2026041510500846000_2026.04.10.717745v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0969-x"},{"key":"2026041510500846000_2026.04.10.717745v1.46","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2026041510500846000_2026.04.10.717745v1.47","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"2026041510500846000_2026.04.10.717745v1.48","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"2026041510500846000_2026.04.10.717745v1.49","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026041510500846000_2026.04.10.717745v1.50","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz369"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.10.717745","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:50:12Z","timestamp":1776275412000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.10.717745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,12]]},"references-count":50,"URL":"https:\/\/doi.org\/10.64898\/2026.04.10.717745","relation":{},"subject":[],"published":{"date-parts":[[2026,4,12]]},"subtype":"preprint"}}