{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:21:03Z","timestamp":1740136863551,"version":"3.37.3"},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21DC010424"],"award-info":[{"award-number":["R21DC010424"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital cytomegalovirus infection is the major nongenetic cause of sensorineural hearing loss at birth and beyond. Among other pathologies, there is a striking dysplasia\/hyperplasia of organ of Corti hair and supporting cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using an in vitro embryonic mouse model of cytomegalovirus\u2010induced cochlear teratogenesis that mimics the known human pathology, and functional signaling network modeling, we tested the hypothesis that cytomegalovirus disrupts the highly ordered organ of Corti hair and supporting cells pattern by dysregulating Notch and Fgfr3, their cognate ligands and downstream effectors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Several novel emergent properties of the critical lateral inhibition subnetwork became apparent. The subnetwork has classic small\u2010world properties such as short paths between most gene pairs, few long\u2010distance links, and considerable clustering. Concomitantly, the calculated probability that our specific gene expression dataset is from dysplastic organs of Corti is highly significant (<jats:italic>p<\/jats:italic>\u2009&lt;\u20091 \u00d7 10<jats:sup>\u221212<\/jats:sup>). Furthermore, we determined that the subnetwork has a highly heterogeneous scale\u2010free topology in which the highly linked genes (hubs),<jats:italic>Notch<\/jats:italic>and<jats:italic>Fgfr3<\/jats:italic>, play a central role in mediating interactions among the less linked genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This phenomenon has important biologic and therapeutic implications. Birth Defects Research (Part A) 103:573\u2013582, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23386","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T20:39:20Z","timestamp":1436906360000},"page":"573-582","source":"Crossref","is-referenced-by-count":1,"title":["CMV\u2010induced embryonic mouse organ of corti dysplasia: Network architecture of dysfunctional lateral inhibition"],"prefix":"10.1002","volume":"103","author":[{"given":"Michael","family":"Melnick","sequence":"first","affiliation":[{"name":"Laboratory Developmental Genetics University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Jaskoll","sequence":"additional","affiliation":[{"name":"Laboratory Developmental Genetics University of Southern California Los Angeles 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