{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:10:23Z","timestamp":1790097023081,"version":"4.0.1"},"reference-count":51,"publisher":"The Company of Biologists","issue":"21","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ragnar S\u00f6derbergs Stiftelse"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Notch signaling patterns the cochlear organ of Corti, and individuals with the JAG1\/NOTCH2-related genetic disorder Alagille syndrome can thus experience hearing loss. We investigated the function of Jag1 in cochlear patterning and signaling using Jag1Ndr\/Ndr mice, which are a model of Alagille syndrome. Jag1Ndr\/Ndr mice exhibited expected vestibular and auditory deficits, a dose-dependent increase in ectopic inner hair cells, and a reduction in outer hair cells. Single cell RNA sequencing of the organ of Corti demonstrated a global dysregulation of genes associated with inner ear development and deafness. Analysis of individual cell types further revealed that Jag1 represses Notch activation in lateral supporting cells and demonstrated a function for Jag1 in gene regulation and development of outer hair cells. Surprisingly, ectopic \u2018outer hair cell-like\u2019 cells were present in the medial compartment and pillar cell region of Jag1Ndr\/Ndr cochleae, yet they exhibited location-dependent expression of the inner hair cell fate-determinant Tbx2, suggesting Jag1 is required for Tbx2 to drive inner hair cell commitment. This study thus identifies new roles for Jag1 in supporting cells, and in outer hair cell specification and positioning.<\/jats:p>","DOI":"10.1242\/dev.202949","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T09:53:51Z","timestamp":1728294831000},"source":"Crossref","is-referenced-by-count":6,"title":["Jag1 represses Notch activation in lateral supporting cells and inhibits an outer hair cell fate in the medial cochlea"],"prefix":"10.1242","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9335-1149","authenticated-orcid":false,"given":"Sandra","family":"de Haan","sequence":"first","affiliation":[{"name":"Karolinska Institutet 1 Department of Cell and Molecular Biology , , Stockholm 17177 ,","place":["Sweden"]},{"name":"National Institute on Deafness and Other Communication Disorders 2 Laboratory of Cochlear Development , , , Bethesda, MD 20892 ,","place":["USA"]},{"name":"National Institutes of Health 2 Laboratory of Cochlear Development , , , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustin A.","family":"Corbat","sequence":"additional","affiliation":[{"name":"Karolinska Institutet 1 Department of Cell and Molecular Biology , , Stockholm 17177 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Cederroth","sequence":"additional","affiliation":[{"name":"Karolinska Institutet 3 Department of Physiology and Pharmacology , , Stockholm 17177 ,","place":["Sweden"]},{"name":"Translational Hearing Research 4 , , Department of Otolaryngology, Head and Neck Surgery , , T\u00fcbingen 72074 ,","place":["Germany"]},{"name":"T\u00fcbingen Hearing Research Center 4 , , Department of Otolaryngology, Head and Neck Surgery , , T\u00fcbingen 72074 ,","place":["Germany"]},{"name":"University of T\u00fcbingen 4 , , Department of Otolaryngology, Head and Neck Surgery , , T\u00fcbingen 72074 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa G.","family":"Autrum","sequence":"additional","affiliation":[{"name":"Karolinska Institutet 1 Department of Cell and Molecular Biology , , Stockholm 17177 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Hankeova","sequence":"additional","affiliation":[{"name":"Karolinska Institutet 1 Department of Cell and Molecular Biology , , Stockholm 17177 ,","place":["Sweden"]},{"name":"Genentech 5 Department of Structural Biology , , South San Francisco, CA 94080 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5618-1053","authenticated-orcid":false,"given":"Elizabeth C.","family":"Driver","sequence":"additional","affiliation":[{"name":"National Institute on Deafness and Other Communication Disorders 2 Laboratory of Cochlear Development , , , Bethesda, MD 20892 ,","place":["USA"]},{"name":"National Institutes of Health 2 Laboratory of Cochlear Development , , , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Canlon","sequence":"additional","affiliation":[{"name":"Karolinska Institutet 3 Department of Physiology and Pharmacology , , Stockholm 17177 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew W.","family":"Kelley","sequence":"additional","affiliation":[{"name":"National Institute on Deafness and Other Communication Disorders 2 Laboratory of Cochlear Development , , , Bethesda, MD 20892 ,","place":["USA"]},{"name":"National Institutes of Health 2 Laboratory of Cochlear Development , , , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8608-625X","authenticated-orcid":false,"given":"Emma R.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Karolinska Institutet 1 Department of Cell and Molecular Biology , , Stockholm 17177 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,11,5]]},"reference":[{"key":"2024110509491724200_DEV202949C1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1086\/345398","article-title":"Identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues","volume":"72","author":"Abe","year":"2003","journal-title":"Am. 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