{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T05:28:06Z","timestamp":1759814886133,"version":"3.41.2"},"reference-count":31,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The choroid plexuses (ChPs) are modified epithelial structures that penetrate all four cerebral ventricles and secrete cerebrospinal fluid. They consist of a central stroma that is vascularized with fenestrated blood vessels and connective tissue. The ChPs are of dual embryonic origin, with forebrain neuroepithelial cells contributing to the epithelial component and mesenchymal cells contributing to the stromal cells. The growth of the ChPs into the ventricular spaces is fueled by the migration and proliferation of neuroepithelial progenitor cells originating from the cortical hem. However, the genetic regulation of neuroepithelial progenitor (NEP) migration during ChP development is not well understood. Here, we report the role of Mllt11 (Af1q\/Tcf7c) in the formation of the ChP in part by regulating the migration of Otx1\/2+ NEPs into the base of the fetal ChP, fueling its \u2018treadmilling\u2019 growth into the lateral ventricle. We used Cux2iresCre\/+ allele to selectively ablate Mllt11 in the developing cortical hem and its principal derivatives, the ChP and hippocampus. We discovered that Mllt11 mutants displayed thickened cuboid epithelial architecture of the ChP but maintained the epithelial organization of the outer layer of the ChP. This likely contributed to shorter lateral ventricle ChP stalks in Mllt11 cKO brains.<\/jats:p>","DOI":"10.1242\/bio.061966","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T05:15:43Z","timestamp":1750828543000},"source":"Crossref","is-referenced-by-count":1,"title":["Altered epithelial development of the lateral ventricle choroid plexus in <i>Mllt11<\/i> mutants"],"prefix":"10.1242","volume":"14","author":[{"given":"Sam","family":"Moore","sequence":"first","affiliation":[{"name":"Dalhousie University, and Brain Repair Centre, Life Science Research Institute Department of Medical Neuroscience, Faculty of Medicine , , 1348 Summer Street, Halifax, Nova Scotia B3H-4R2 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Stanton-Turcotte","sequence":"additional","affiliation":[{"name":"Dalhousie University, and Brain Repair Centre, Life Science Research Institute Department of Medical Neuroscience, Faculty of Medicine , , 1348 Summer Street, Halifax, Nova Scotia B3H-4R2 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily A.","family":"Witt","sequence":"additional","affiliation":[{"name":"Dalhousie University, and Brain Repair Centre, Life Science Research Institute Department of Medical Neuroscience, Faculty of Medicine , , 1348 Summer Street, Halifax, Nova Scotia B3H-4R2 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0712-4295","authenticated-orcid":false,"given":"Angelo","family":"Iulianella","sequence":"additional","affiliation":[{"name":"Dalhousie University, and Brain Repair Centre, Life Science Research Institute Department of Medical Neuroscience, Faculty of Medicine , , 1348 Summer Street, Halifax, Nova Scotia B3H-4R2 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"2025072108364788700_BIO061966C1","first-page":"669","article-title":"The role of Otx and Otp genes in brain development","volume":"44","author":"Acampora","year":"2000","journal-title":"Int. J. Dev. Biol."},{"key":"2025072108364788700_BIO061966C2","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1002\/dvdy.540","article-title":"Retinal neuroblast migration and ganglion cell layer organization require the cytoskeletal-interacting protein Mllt11","volume":"252","author":"Blommers","year":"2023","journal-title":"Dev. Dyn."},{"key":"2025072108364788700_BIO061966C3","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1002\/dneu.22936","article-title":"Cerebellar granule cell migration and folia development require Mllt11\/Af1q\/Tcf7c","volume":"84","author":"Blommers","year":"2024","journal-title":"Dev. Neurobiol."},{"key":"2025072108364788700_BIO061966C4","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/S0925-4773(00)00515-3","article-title":"LIM-homeodomain gene Lhx2 regulates the formation of the cortical hem","volume":"100","author":"Bulchand","year":"2001","journal-title":"Mech. Dev."},{"key":"2025072108364788700_BIO061966C5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2018.02.046","article-title":"Lhx2, an evolutionarily conserved, multifunctional regulator of forebrain development","volume":"1705","author":"Chou","year":"2019","journal-title":"Brain Res."},{"key":"2025072108364788700_BIO061966C6","doi-asserted-by":"publisher","first-page":"C519","DOI":"10.1152\/ajpcell.00305.2017","article-title":"Choroid plexus epithelial cells express the adhesion protein P-cadherin at cell-cell contacts and syntaxin-4 in the luminal membrane domain","volume":"314","author":"Christensen","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2025072108364788700_BIO061966C7","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/1097-0029(20010101)52:1&lt;5::AID-JEMT3&gt;3.0.CO;2-J","article-title":"Development of the choroid plexus","volume":"52","author":"Dziegielewska","year":"2001","journal-title":"Microsc. Res. Tech."},{"key":"2025072108364788700_BIO061966C8","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1002\/cne.10661","article-title":"Structural characteristics and barrier properties of the choroid plexuses in developing brain of the opossum (Monodelphis Domestica)","volume":"460","author":"Ek","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"2025072108364788700_BIO061966C9","doi-asserted-by":"publisher","first-page":"dev170068","DOI":"10.1242\/dev.170068","article-title":"Lmx1a drives Cux2 expression in the cortical hem through activation of a conserved intronic enhancer","volume":"146","author":"Fregoso","year":"2019","journal-title":"Development"},{"key":"2025072108364788700_BIO061966C10","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/(SICI)1097-0029(19980415)41:2&lt;124::AID-JEMT3&gt;3.0.CO;2-U","article-title":"Ependymal and choroidal cells in culture: characterization and functional differentiation","volume":"41","author":"Gabrion","year":"1998","journal-title":"Microsc. Res. Tech."},{"key":"2025072108364788700_BIO061966C11","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s00401-018-1807-1","article-title":"Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease","volume":"135","author":"Ghersi-Egea","year":"2018","journal-title":"Acta Neuropathol."},{"key":"2025072108364788700_BIO061966C12","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1242\/dev.125.12.2315","article-title":"The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice","volume":"125","author":"Grove","year":"1998","journal-title":"Development"},{"key":"2025072108364788700_BIO061966C13","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":"2025072108364788700_BIO061966C14","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1242\/dev.013276","article-title":"Cux2 (Cutl2) integrates neural progenitor development with cell-cycle progression during spinal cord neurogenesis","volume":"135","author":"Iulianella","year":"2008","journal-title":"Development"},{"key":"2025072108364788700_BIO061966C15","doi-asserted-by":"publisher","first-page":"340","DOI":"10.3389\/fnins.2014.00340","article-title":"The choroid plexuses and their impact on developmental neurogenesis","volume":"8","author":"Johansson","year":"2014","journal-title":"Front. Neurosci."},{"key":"2025072108364788700_BIO061966C16","doi-asserted-by":"publisher","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":"2025072108364788700_BIO061966C17","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1369\/jhc.2010.955757","article-title":"Expression of the homeobox genes OTX2 and OTX1 in the early developing human brain","volume":"58","author":"Larsen","year":"2010","journal-title":"J. Histochem. Cytochem."},{"key":"2025072108364788700_BIO061966C18","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":"2025072108364788700_BIO061966C19","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1743-8454-7-16","article-title":"Development of the lateral ventricular choroid plexus in a marsupial, Monodelphis domestica","volume":"7","author":"Liddelow","year":"2010","journal-title":"Cerebrospinal Fluid Res."},{"key":"2025072108364788700_BIO061966C20","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":"2025072108364788700_BIO061966C21","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1091\/mbc.e05-07-0650","article-title":"Zonula occludens-1 function in the assembly of tight junctions in Madin-Darby canine kidney epithelial cells","volume":"17","author":"Mcneil","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"2025072108364788700_BIO061966C22","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/S0896-6273(01)00504-9","article-title":"Patterning of the dorsal telencephalon and cerebral cortex by a roof plate-Lhx2 pathway","volume":"32","author":"Monuki","year":"2001","journal-title":"Neuron"},{"key":"2025072108364788700_BIO061966C23","doi-asserted-by":"publisher","first-page":"210042","DOI":"10.1098\/rsob.210042","article-title":"Development of the mammalian cortical hem and its derivatives: the choroid plexus, Cajal-Retzius cells and hippocampus","volume":"11","author":"Moore","year":"2021","journal-title":"Open Biol."},{"key":"2025072108364788700_BIO061966C24","doi-asserted-by":"publisher","first-page":"4120","DOI":"10.1523\/JNEUROSCI.5185-09.2010","article-title":"Pals1 is a major regulator of the epithelial-like polarization and the extension of the myelin sheath in peripheral nerves","volume":"30","author":"Ozcelik","year":"2010","journal-title":"J. Neurosci."},{"key":"2025072108364788700_BIO061966C25","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/0736-5748(90)90050-C","article-title":"Choroidal ependymocytes in culture: expression of markers of polarity and function","volume":"8","author":"Peraldi-Roux","year":"1990","journal-title":"Int. J. Dev. Neurosci."},{"key":"2025072108364788700_BIO061966C26","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1093\/cercor\/bhs421","article-title":"Lhx2 regulates the development of the forebrain hem system","volume":"24","author":"Roy","year":"2014","journal-title":"Cereb. Cortex"},{"key":"2025072108364788700_BIO061966C27","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"2025072108364788700_BIO061966C28","doi-asserted-by":"publisher","first-page":"3931","DOI":"10.1523\/JNEUROSCI.0124-22.2022","article-title":"Mllt11 regulates migration and neurite outgrowth of cortical projection neurons during development","volume":"42","author":"Stanton-Turcotte","year":"2022","journal-title":"J. Neurosci."},{"key":"2025072108364788700_BIO061966C29","doi-asserted-by":"publisher","first-page":"9805","DOI":"10.1523\/JNEUROSCI.0967-12.2012","article-title":"Matrix metalloprotease 8-dependent extracellular matrix cleavage at the blood-CSF barrier contributes to lethality during systemic inflammatory diseases","volume":"32","author":"Vandenbroucke","year":"2012","journal-title":"J. Neurosci."},{"key":"2025072108364788700_BIO061966C30","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.gep.2014.05.001","article-title":"MLLT11\/AF1q is differentially expressed in maturing neurons during development","volume":"15","author":"Yamada","year":"2014","journal-title":"Gene Expr. Patterns"},{"key":"2025072108364788700_BIO061966C31","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/hipo.22370","article-title":"Cux2 activity defines a subpopulation of perinatal neurogenic progenitors in the hippocampus","volume":"25","author":"Yamada","year":"2015","journal-title":"Hippocampus"}],"container-title":["Biology Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.061966\/3653887\/bio061966.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.061966\/3657612\/bio061966.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.061966\/3657612\/bio061966.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T12:36:52Z","timestamp":1753101412000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/bio\/article\/14\/7\/bio061966\/368634\/Altered-epithelial-development-of-the-lateral"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,15]]},"references-count":31,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7,15]]}},"URL":"https:\/\/doi.org\/10.1242\/bio.061966","relation":{},"ISSN":["2046-6390"],"issn-type":[{"type":"electronic","value":"2046-6390"}],"subject":[],"published":{"date-parts":[[2025,7,15]]},"article-number":"bio061966"}}