{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T17:11:15Z","timestamp":1760980275693,"version":"build-2065373602"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,3,11]],"date-time":"2005-03-11T00:00:00Z","timestamp":1110499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fibroblast growth factor (FGF) signaling is crucial for the induction and growth of the ear, a sensory organ that involves intimate tissue interactions. Here, we report the abnormality of <jats:italic>Fgf10<\/jats:italic> null ear and the identification of a <jats:italic>cis<\/jats:italic>\u2010regulatory element directing otic expression of <jats:italic>Fgf10<\/jats:italic>. In <jats:italic>Fgf10<\/jats:italic> null inner ears, we found that the initial development of semicircular, vestibular, and cochlear divisions is roughly normal, after which there are abnormalities of semicircular canal\/cristae and vestibular development. The mutant semicircular disks remain without canal formation by the perinatal stage. To elucidate regulation of the <jats:italic>Fgf10<\/jats:italic> expression during inner ear development, we isolated a 6.6\u2010kb fragment of its 5\u2032\u2010upstream region and examined its transcriptional activity with transgenic mice, using a <jats:italic>lacZ<\/jats:italic>\u2010reporter system. From comparison of the mouse sequences of the 6.6\u2010kb fragment with corresponding sequences of the human and chicken <jats:italic>Fgf10<\/jats:italic>, we identified a 0.4\u2010kb enhancer sequence that drives <jats:italic>Fgf10<\/jats:italic> expression in the developing inner ear. The enhancer sequences have motifs for many homeodomain\u2010containing proteins (e.g., Prx, Hox, Nkx), in addition to POU\u2010domain factors (e.g., Brn3), zinc\u2010finger transcription factors (e.g., GATA\u2010binding factors), TCF\/LEF\u20101, and a SMAD\u2010interacting protein. Thus, FGF10 signaling is dispensable for specification of otic compartment identity but is required for hollowing the semicircular disk. Furthermore, the analysis of a putative inner ear enhancer of <jats:italic>Fgf10<\/jats:italic> has disclosed a complicated regulation of <jats:italic>Fgf10<\/jats:italic> during inner ear development by numerous transcription factors and signaling pathways. Developmental Dynamics 233:177\u2013187, 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.20319","type":"journal-article","created":{"date-parts":[[2005,3,11]],"date-time":"2005-03-11T17:48:24Z","timestamp":1110563304000},"page":"177-187","source":"Crossref","is-referenced-by-count":44,"title":["Identification of <i>cis<\/i>\u2010element regulating expression of the mouse <i>Fgf10<\/i> gene during inner ear 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