{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:30:17Z","timestamp":1777444217295,"version":"3.51.4"},"reference-count":38,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[2020,9,5]],"date-time":"2020-09-05T00:00:00Z","timestamp":1599264000000},"content-version":"vor","delay-in-days":568,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and other Communication Disorders","doi-asserted-by":"publisher","award":["1ZIADC000021"],"award-info":[{"award-number":["1ZIADC000021"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The semicircular canals of the mammalian inner ear are derived from epithelial pouches in which epithelial cells in the central region of each pouch undergo resorption, leaving behind the region at the rim to form a tube-shaped canal. Lack of proliferation at the rim and\/or over-clearing of epithelial cells in the center of the pouch can obliterate canal formation. Otic-specific knockout of bone morphogenetic protein 2 (Bmp2) results in absence of all three semicircular canals; however, the common crus and ampullae housing the sensory tissue (crista) are intact. The lack of Bmp2 causes Ntn1 (which encodes netrin 1), which is required for canal resorption, to be ectopically expressed at the canal rim. Ectopic Ntn1 results in reduction of Dlx5 and Lmo4, which are required for rim formation. These phenotypes can be partially rescued by removing one allele of Ntn1 in the Bmp2 mutants, indicating that Bmp2 normally negatively regulates Ntn1 for canal formation. Additionally, non-resorption of the canal pouch in Ntn1\u2212\/\u2212 mutants is partially rescued by removing one allele of Bmp2. Thus, reciprocal inhibition between Bmp2 and netrin 1 is involved in canal formation of the vestibule.<\/jats:p>","DOI":"10.1242\/dev.174748","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T19:14:27Z","timestamp":1550258067000},"source":"Crossref","is-referenced-by-count":14,"title":["Genetic interactions support an inhibitory relationship between bone morphogenetic protein 2 and netrin 1 during semicircular canal formation"],"prefix":"10.1242","volume":"146","author":[{"given":"Chan Ho","family":"Hwang","sequence":"first","affiliation":[{"name":"National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Porter Neuroscience Research Center , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Keller","sequence":"additional","affiliation":[{"name":"National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Porter Neuroscience Research Center , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Renner","sequence":"additional","affiliation":[{"name":"National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Porter Neuroscience Research Center , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2421-8093","authenticated-orcid":false,"given":"Sho","family":"Ohta","sequence":"additional","affiliation":[{"name":"National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Porter Neuroscience Research Center , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1400-3558","authenticated-orcid":false,"given":"Doris K.","family":"Wu","sequence":"additional","affiliation":[{"name":"National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Porter Neuroscience Research Center , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2019,2,15]]},"reference":[{"key":"2024061300261094800_DEV174748C1","doi-asserted-by":"publisher","first-page":"4091","DOI":"10.1242\/dev.029330","article-title":"Cross-repressive interactions between Lrig3 and netrin 1 shape the architecture of the inner ear","volume":"135","author":"Abraira","year":"2008","journal-title":"Development"},{"key":"2024061300261094800_DEV174748C2","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1006\/dbio.1999.9457","article-title":"Ectopic noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear","volume":"216","author":"Chang","year":"1999","journal-title":"Dev. 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