{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T05:05:31Z","timestamp":1762059931292,"version":"build-2065373602"},"reference-count":71,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP180100017","APP1141928"],"award-info":[{"award-number":["DP180100017","APP1141928"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["DP180100017","APP1141928"],"award-info":[{"award-number":["DP180100017","APP1141928"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian Government","award":["DP180100017","APP1141928"],"award-info":[{"award-number":["DP180100017","APP1141928"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nuclear factor one X (NFIX) is a transcription factor required for normal ependymal development. Constitutive loss of Nfix in mice (Nfix\u2212\/\u2212) is associated with hydrocephalus and sloughing of the dorsal ependyma within the lateral ventricles. Previous studies have implicated NFIX in the transcriptional regulation of genes encoding for factors essential to ependymal development. However, the cellular and molecular mechanisms underpinning hydrocephalus in Nfix\u2212\/\u2212 mice are unknown. To investigate the role of NFIX in hydrocephalus, we examined ependymal cells in brains from postnatal Nfix\u2212\/\u2212 and control (Nfix+\/+) mice using a combination of confocal and electron microscopy. This revealed that the ependymal cells in Nfix\u2212\/\u2212 mice exhibited abnormal cilia structure and disrupted localisation of adhesion proteins. Furthermore, we modelled ependymal cell adhesion using epithelial cell culture and revealed changes in extracellular matrix and adherens junction gene expression following knockdown of NFIX. Finally, the ablation of Nfix from ependymal cells in the adult brain using a conditional approach culminated in enlarged ventricles, sloughing of ependymal cells from the lateral ventricles and abnormal localisation of adhesion proteins, which are phenotypes observed during development. Collectively, these data demonstrate a pivotal role for NFIX in the regulation of cell adhesion within ependymal cells of the lateral ventricles.<\/jats:p>","DOI":"10.3390\/cells11152377","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T21:41:37Z","timestamp":1659476497000},"page":"2377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hydrocephalus in Nfix\u2212\/\u2212 Mice Is Underpinned by Changes in Ependymal Cell Physiology"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5284-4617","authenticated-orcid":false,"given":"Danyon","family":"Harkins","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracey J.","family":"Harvey","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cooper","family":"Atterton","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Miller","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8164-2408","authenticated-orcid":false,"given":"Laura","family":"Currey","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Oishi","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Kasherman","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul Ayala","family":"Davila","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Harris","sequence":"additional","affiliation":[{"name":"Centre for Microscopy and Microanalysis, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Green","sequence":"additional","affiliation":[{"name":"Centre for Microscopy and Microanalysis, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Piper","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7494-5248","authenticated-orcid":false,"given":"Robert G.","family":"Parton","sequence":"additional","affiliation":[{"name":"Centre for Microscopy and Microanalysis, The University of Queensland, Brisbane 4072, Australia"},{"name":"Institute for Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Thor","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen M.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Piper","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"},{"name":"Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.celrep.2019.01.088","article-title":"Development of Ependymal and Postnatal Neural Stem Cells and Their Origin from a Common Embryonic Progenitor","volume":"27","author":"Redmond","year":"2019","journal-title":"Cell 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