{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:24Z","timestamp":1792790364472,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,23]]},"group-title":"Neuroscience","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institute on Deafness and Other Communication Disorders","award":["U24-DC020849"],"award-info":[{"award-number":["U24-DC020849"]}],"id":[{"id":"https:\/\/ror.org\/04mhx6838","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04g3dn724","id-type":"ROR","asserted-by":"publisher"}]},{"name":"The Meyer-Hirsch Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Many falls and balance disorders in older adults originate in the otolith organs, the gravity sensors of the inner ear. These sensors maintain upright posture through otoconia, calcium carbonate crystals that mass-load the sensory maculae. Otoconia dislodgement causes the most common form of vertigo, and their age-related loss reduces gravity sensation and undermines balance. Yet the cellular mechanisms of otoconia formation and maintenance\u2014and how they fail in disease\u2014 remain unknown. Using mineral-preserving histology, crystal-sensitive imaging, volume electron microscopy, and immunolabeling in human and animal otolith organs, we found otoconia biogenesis\u2013related proteins and early crystallization at the pole opposing the macula, the roof domain. We discovered filigree extracellular matrix scaffolds bridging roof and macula, loaded with nascent otoconia, suggesting scaffold-guided transport across the organ. Single-cell transcriptomics nominated a specialized roof mesenchyme signaling to the roof epithelium as a driver of otoconia and scaffold production. In guinea pigs with endolymphatic hydrops, fluid expansion of the organs ruptured the otoconia-trafficking scaffolds as roof and macula separated, followed by a decline in macular otoconial mass. We propose a new disease model for common vertigo and balance disorders in which disruption of the otoconia-generating and -trafficking epithelial-mesenchymal roof niche leads to displacement and depletion of otoconia.<\/jats:p>","DOI":"10.64898\/2026.09.16.752180","type":"posted-content","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:25:22Z","timestamp":1790187922000},"source":"Crossref","is-referenced-by-count":0,"title":["Disruption of a structural niche for otoconia maintenance may underlie common vestibular disorders"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3705-6162","authenticated-orcid":false,"given":"Diana M.","family":"Correa","sequence":"first","affiliation":[{"name":"Otopathology Laboratory, Mass Eye and Ear, Boston, MA, USA"},{"name":"Eaton-Peabody Laboratories, Mass Eye and Ear, Boston, MA, USA"},{"name":"Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel P.","family":"David","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Northwestern Medicine, Chicago, IL, USA"},{"name":"Feinberg School of Medicine, Northwestern University, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Epithelial Biology Center, Vanderbilt Center for Stem Cell Biology, Center for Computational Systems Biology, Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Osgood","sequence":"additional","affiliation":[{"name":"Eaton-Peabody Laboratories, Mass Eye and Ear, Boston, MA, USA"},{"name":"Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur A.","family":"Indzhykulian","sequence":"additional","affiliation":[{"name":"Eaton-Peabody Laboratories, Mass Eye and Ear, Boston, MA, USA"},{"name":"Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Kr\u00e4mer","sequence":"additional","affiliation":[{"name":"Center for Nanoscale Systems, Harvard University, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha A.","family":"Jan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Epithelial Biology Center, Vanderbilt Center for Stem Cell Biology, Center for Computational Systems Biology, Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas H.","family":"Eckhard","sequence":"additional","affiliation":[{"name":"Otopathology Laboratory, Mass Eye and Ear, Boston, MA, USA"},{"name":"Eaton-Peabody Laboratories, Mass Eye and Ear, Boston, MA, USA"},{"name":"Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092910203373000_2026.09.16.752180v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joto.2018.11.006"},{"key":"2026092910203373000_2026.09.16.752180v2.2","unstructured":"World Health Organization. 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