Deletion of Brg1 causes stereocilia bundle fusion and cuticular plate loss in vestibular hair cells

被引：4
作者：
Jin, Yecheng [1 ,2 ]
Gao, Xiaotong [1 ,2 ]
Fu, Xiaolong [1 ,2 ]
Li, Shiwei [1 ,2 ]
Sun, Xiaoyang [1 ,2 ]
Gao, Jiangang [1 ,2 ]
机构：
[1] Shandong Univ, Sch Life Sci, 27 Shanda Nanlu, Jinan 250100, Peoples R China
[2] Shandong Univ, Minist Educ Expt Teratol, Key Lab, Jinan 250100, Peoples R China
来源：
HEARING RESEARCH | 2019年 / 377卷
基金：
中国博士后科学基金;
关键词：
Brg1; Vestibule; Hair cell; Stereocilia bundle; Cuticular plate; SWI/SNF COMPLEXES; MYOSIN VI; PROLIFERATION; PLAYS;
D O I：
10.1016/j.heares.2019.04.002
中图分类号：
R36 [病理学]; R76 [耳鼻咽喉科学];
学科分类号：
100104 ; 100213 ;
摘要：
Brg1 is an ATPase subunit of the SWI/SNF chromatin-remodeling complex, and it is indispensable for the development and homeostasis of various organs. Conditional deletion of Brg1 in cochlea hair cells (HCs) leads to multiple structural defects and profound deafness. However, the premature death of Brg1-deficient cochlea HCs hindered further study of the role of Brg1. In contrast to cochlea HCs, Brg1-deficient vestibular HCs survived for a long time. Therefore, HC apical structure and vestibular function were examined in inner HC-specific conditional Brg1 knockout mice. Vestibular HCs exhibited fused and elongated stereocilia bundles after deletion of Brg1, and the cuticular plate was absent in most HCs with fused stereocilia bundles. HC loss was observed in conditional Brg1 knockout mice at the age of 12 months. Morphological defects and HC loss were primarily restricted in the striolar region of the utricle and saccule and in the central region of ampulla. The behavioral tests revealed that Brg1 deletion in HCs caused vestibular dysfunction in older adult mice. These results suggest that Brg1 may play specific roles in the maintenance of the HC stereocilia bundle and the cuticular plate. (C) 2019 Elsevier B.V. All rights reserved.
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收藏
页码：247 / 259
页数：13
相关论文
共 35 条
[1]   Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma [J].
Aldiri, Issam ;
Ajioka, Itsuki ;
Xu, Beisi ;
Zhang, Jiakun ;
Chen, Xiang ;
Benavente, Claudia ;
Finkelstein, David ;
Johnson, Dianna ;
Akiyama, Jennifer ;
Pennacchio, Len A. ;
Dyer, Michael A. .
DEVELOPMENT, 2015, 142 (23) :4092-4106
[2]   A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes [J].
Bultman, S ;
Gebuhr, T ;
Yee, D ;
La Mantia, C ;
Nicholson, J ;
Gilliam, A ;
Randazzo, F ;
Metzger, D ;
Chambon, P ;
Crabtree, G ;
Magnuson, T .
MOLECULAR CELL, 2000, 6 (06) :1287-1295
[3]   Single-cell RNA-Seq resolves cellular complexity in sensory organs from the neonatal inner ear [J].
Burns, Joseph C. ;
Kelly, Michael C. ;
Hoa, Michael ;
Morell, Robert J. ;
Kelley, Matthew W. .
NATURE COMMUNICATIONS, 2015, 6
[4]   Over Half the Hair Cells in the Mouse Utricle First Appear After Birth, with Significant Numbers Originating from Early Postnatal Mitotic Production in Peripheral and Striolar Growth Zones [J].
Burns, Joseph C. ;
On, Doan ;
Baker, Wendy ;
Collado, M. Sol ;
Corwin, Jeffrey T. .
JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY, 2012, 13 (05) :609-627
[5]   The Postnatal Accumulation of Junctional E-Cadherin Is Inversely Correlated with the Capacity for Supporting Cells to Convert Directly into Sensory Hair Cells in Mammalian Balance Organs [J].
Collado, Maria Sol ;
Thiede, Benjamin R. ;
Baker, Wendy ;
Askew, Charles ;
Igbani, Lisa M. ;
Corwin, Jeffrey T. .
JOURNAL OF NEUROSCIENCE, 2011, 31 (33) :11855-11866
[6]   THE STRUCTURE OF THE CUTICULAR PLATE, AN INVIVO ACTIN GEL [J].
DEROSIER, DJ ;
TILNEY, LG .
JOURNAL OF CELL BIOLOGY, 1989, 109 (06) :2853-2867
[7]   Alternative Splice Forms Influence Functions of Whirlin in Mechanosensory Hair Cell Stereocilia [J].
Ebrahim, Seham ;
Ingham, Neil J. ;
Lewis, Morag A. ;
Rogers, Michael J. C. ;
Cui, Runjia ;
Kachar, Bechara ;
Pass, Johanna C. ;
Steel, Karen P. .
CELL REPORTS, 2016, 15 (05) :935-943
[8]   Hair Bundle Defects and Loss of Function in the Vestibular End Organs of Mice Lacking the Receptor-Like Inositol Lipid Phosphatase PTPRQ [J].
Goodyear, Richard J. ;
Jones, Sherri M. ;
Sharifi, Louise ;
Forge, Andy ;
Richardson, Guy P. .
JOURNAL OF NEUROSCIENCE, 2012, 32 (08) :2762-2772
[9]   The chromatin-remodeling enzyme BRG1 plays an essential role in primitive erythropoiesis and vascular development [J].
Griffin, Courtney T. ;
Brennan, Jennifer ;
Magnuson, Terry .
DEVELOPMENT, 2008, 135 (03) :493-500
[10]   Chromatin regulation by Brg1 underlies heart muscle development and disease [J].
Hang, Calvin T. ;
Yang, Jin ;
Han, Pei ;
Cheng, Hsiu-Ling ;
Shang, Ching ;
Ashley, Euan ;
Zhou, Bin ;
Chang, Ching-Pin .
NATURE, 2010, 466 (7302) :62-U74
1234