title: Pax3 function is required specifically for inner ear structures with melanogenic fates.
abstract: Pax3 mutations result in malformed inner ears in Splotch mutant mice and hearing loss in humans with Waardenburg's syndrome type I. In the inner ear, Pax3 is thought to be involved mainly in the development of neural crest. However, recent studies have shown that Pax3-expressing cells contribute extensively to multiple inner ear structures, some of which were considered to be derived from the otic epithelium. To examine the specific functions of Pax3 during inner ear development, fate mapping of Pax3 lineage was performed in the presence or absence of functional Pax3 proteins using Pax3(Cre) knock-in mice bred to Rosa26 reporter (R26R) line. β-gal-positive cells were widely distributed in Pax3(Cre/+); R26R inner ears at embryonic day (E) 15.5, including the endolymphatic duct, common crus, cristae, maculae, cochleovestibular ganglion, and stria vascularis. In the absence of Pax3 in Pax3(Cre/Cre); R26R inner ears, β-gal-positive cells disappeared from regions with melanocytes such as the stria vascularis of the cochlea and dark cells in the vestibule. Consistently, the expression of Dct, a melanoblast marker, was also absent in the mutant inner ears. However, when examined at E11.5, β-gal positive cells were present in Pax3(Cre/Cre) mutant otocysts, whereas Dct expression was absent, suggesting that Pax3 lineage with a melanogenic fate migrated to the inner ear, yet failed to differentiate and survive without Pax3 function. Gross inner ear morphology was generally normal in Pax3(Cre/Cre) mutants, unless neural tube defects extended to the cranial region. Taken together, these results suggest that despite the extensive contribution of Pax3-expressing cells to multiple inner ear tissues, Pax3 function is required specifically for inner ear components with melanogenic fates.
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Hongkyung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Harinarayana
authors.initials: H
authors.lastname: Ankamreddy
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Kyoung-Ah
authors.initials: KA
authors.lastname: Kong
authors.affiliation: College of Pharmacy, Dongguk University, Goyangsi, Gyeonggido 410-820, Republic of Korea.
authors.forename: Hyuk Wan
authors.initials: HW
authors.lastname: Ko
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea. Electronic address: bokj@yuhs.ac.
authors.forename: Jinwoong
authors.initials: J
authors.lastname: Bok
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D007758:Ear, Inner / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009432:Neural Crest / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; C068686:Pax3 protein, mouse
keywords: Hearing loss; Inner ear; Melanocyte; Neural crest; Pax3