title: Septin7 regulates inner ear formation at an early developmental stage.
abstract: Septins are guanosine triphosphate-binding proteins that are evolutionally conserved in all eukaryotes other than plants. They function as multimeric complexes that interact with membrane lipids, actomyosin, and microtubules. Based on these interactions, septins play essential roles in the morphogenesis and physiological functions of many mammalian cell types including the regulation of microtubule stability, vesicle trafficking, cortical rigidity, planar cell polarity, and apoptosis. The inner ear, which perceives auditory and equilibrium sensation with highly differentiated hair cells, has a complicated gross morphology. Furthermore, its development including morphogenesis is dependent on various molecular mechanisms, such as apoptosis, convergent extension, and cell fate determination. To determine the roles of septins in the development of the inner ear, we specifically deleted Septin7 (Sept7), the non-redundant subunit in the canonical septin complex, in the inner ear at different times during development. Foxg1Cre-mediated deletion of Sept7, which achieved the complete knockout of Sept7 within the inner ear at E9.5, caused cystic malformation of inner ears and a reduced numbers of sensory epithelial cells despite the existence of mature hair cells. Excessive apoptosis was observed at E10.5,E11.5 and E12.5 in all inner ear epithelial cells and at E10.5 and E11.5 in prosensory epithelial cells of the inner ears of Foxg1Cre;Septin7floxed/floxedmice. In contrast with apoptosis, cell proliferation in the inner ear did not significantly change between control and mutant mice. Deletion of Sept7 within the cochlea at a later stage (around E15.5) with Emx2Cre did not result in any apparent morphological anomalies observed in Foxg1Cre;Septin7floxed/floxedmice. These results suggest that SEPT7 regulates gross morphogenesis of the inner ear and maintains the size of the inner ear sensory epithelial area and exerts its effects at an early developmental stage of the inner ear.
authors.affiliation: Department Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Torii
authors.affiliation: Department of Otolaryngology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama 710-8602, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Department Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Katsuno
authors.affiliation: Department Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Shiga Medical Center Research Institute, 5-4-30, Moriyama, Moriyama, Shiga 524-8524, Japan.
authors.forename: Juichi
authors.initials: J
authors.lastname: Ito
authors.affiliation: Department Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Omori
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Department Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: yamamoto@ent.kuhp.kyoto-u.ac.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D003056:Cochlear Nerve / Q000196:embryology; D007758:Ear, Inner / Q000002:abnormalities / Q000196:embryology* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009024:Morphogenesis; D018995:Myosin Heavy Chains / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis; D009929:Organ Size; D055748:SOXB1 Transcription Factors / Q000032:analysis; D058112:Septins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C089785:myosin VI; C512895:Sept7 protein, mouse; D058112:Septins; D018995:Myosin Heavy Chains
keywords: Gross morphogenesis; Hair cell differentiation; Inner ear; Septin