title: Deletion of Brg1 causes abnormal hair cell planer polarity, hair cell anchorage, and scar formation in mouse cochlea.
abstract: Hair cells (HCs) are mechanosensors that play crucial roles in perceiving sound, acceleration, and fluid motion. The precise architecture of the auditory epithelium and its repair after HC loss is indispensable to the function of organ of Corti (OC). In this study, we showed that Brg1 was highly expressed in auditory HCs. Specific deletion of Brg1 in postnatal HCs resulted in rapid HC degeneration and profound deafness in mice. Further experiments showed that cell-intrinsic polarity of HCs was abolished, docking of outer hair cells (OHCs) by Deiter's cells (DCs) failed, and scar formation in the reticular lamina was deficient. We demonstrated that Brg1 ablation disrupted the Gαi/Insc/LGN and aPKC asymmetric distributions, without overt effects on the core planer cell polarity (PCP) pathway. We also demonstrated that Brg1-deficient HCs underwent apoptosis, and that leakage in the reticular lamina caused by deficient scar formation shifted the mode of OHC death from apoptosis to necrosis. Together, these data demonstrated a requirement for Brg1 activity in HC development and suggested a role for Brg1 in the proper cellular structure formation of HCs.
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Yecheng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Naixia
authors.initials: N
authors.lastname: Ren
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Fu
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Sun
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Men
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Second Hospital of Shandong University, Jinan 250033, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xia
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D016764:Cell Polarity; D002921:Cicatrix / Q000235:genetics* / Q000378:metabolism; D003051:Cochlea / Q000293:injuries*; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D003638:Deafness / Q000235:genetics*; D017353:Gene Deletion; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009336:Necrosis; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases