Deletion of Brg1 causes abnormal hair cell planer polarity, hair cell anchorage, and scar formation in mouse cochlea

被引:7
作者
Jin, Yecheng [1 ,2 ]
Ren, Naixia [1 ,2 ]
Li, Shiwei [1 ,2 ]
Fu, Xiaolong [1 ,2 ]
Sun, Xiaoyang [1 ,2 ]
Men, Yuqin [1 ,2 ]
Xu, Zhigang [1 ,2 ]
Zhang, Jian [1 ,2 ]
Xie, Yue [1 ,2 ]
Xia, Ming [3 ]
Gao, Jiangang [1 ,2 ]
机构
[1] Shandong Univ, Sch Life Sci, Minist Educ Expt Teratol, Jinan 250100, Peoples R China
[2] Shandong Univ, Key Lab, Minist Educ Expt Teratol, Jinan 250100, Peoples R China
[3] Shandong Univ, Hosp 2, Dept Otolaryngol Head & Neck Surg, Jinan 250033, Peoples R China
基金
中国国家自然科学基金;
关键词
INTERCELLULAR-JUNCTIONS; RETINOBLASTOMA PROTEIN; RETICULAR LAMINA; TIGHT JUNCTIONS; ORGAN; INNER; APOPTOSIS; CILIARY; DEGENERATION; ORGANIZATION;
D O I
10.1038/srep27124
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 Gai/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.
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页数:14
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共 63 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]   How to Bury the Dead: Elimination of Apoptotic Hair Cells from the Hearing Organ of the Mouse [J].
Anttonen, Tommi ;
Belevich, Ilya ;
Kirjavainen, Anna ;
Laos, Maarja ;
Brakebusch, Cord ;
Jokitalo, Eija ;
Pirvola, Ulla .
JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY, 2014, 15 (06) :975-992
[3]   Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood [J].
Anttonen, Tommi ;
Kirjavainen, Anna ;
Belevich, Ilya ;
Laos, Maarja ;
Richardson, William D. ;
Jokitalo, Eija ;
Brakebusch, Cord ;
Pirvola, Ulla .
SCIENTIFIC REPORTS, 2012, 2
[4]   Tissue-specific SMARCA4 binding at active and repressed regulatory elements during embryogenesis [J].
Attanasio, Catia ;
Nord, Alex S. ;
Zhu, Yiwen ;
Blow, Matthew J. ;
Biddie, Simon C. ;
Mendenhall, Eric M. ;
Dixon, Jesse ;
Wright, Crystal ;
Hosseini, Roya ;
Akiyama, Jennifer A. ;
Holt, Amy ;
Plajzer-Frick, Ingrid ;
Shoukry, Malak ;
Afzal, Veena ;
Ren, Bing ;
Bernstein, Bradley E. ;
Rubin, Edward M. ;
Visel, Axel ;
Pennacchio, Len A. .
GENOME RESEARCH, 2014, 24 (06) :920-929
[5]   BRG1 Mutations Found in Human Cancer Cell Lines Inactivate Rb-Mediated Cell-Cycle Arrest [J].
Bartlett, Christopher ;
Orvis, Tess J. ;
Rosson, Gary S. ;
Weissman, Bernard E. .
JOURNAL OF CELLULAR PHYSIOLOGY, 2011, 226 (08) :1989-1997
[6]   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
[7]   A historical to present-day account of efforts to answer the question: "What puts the brakes on mammalian hair cell regeneration?" [J].
Burns, Joseph C. ;
Corwin, Jeffrey T. .
HEARING RESEARCH, 2013, 297 :52-67
[8]   Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse [J].
Curtin, JA ;
Quint, E ;
Tsipouri, V ;
Arkell, RM ;
Cattanach, B ;
Copp, AJ ;
Henderson, DJ ;
Spurr, N ;
Stanier, P ;
Fisher, EM ;
Nolan, PM ;
Steel, KP ;
Brown, SDM ;
Gray, IC ;
Murdoch, JN .
CURRENT BIOLOGY, 2003, 13 (13) :1129-1133
[9]   THE RETINOBLASTOMA PROTEIN AND BRG1 FORM A COMPLEX AND COOPERATE TO INDUCE CELL-CYCLE ARREST [J].
DUNAIEF, JL ;
STROBER, BE ;
GUHA, S ;
KHAVARI, PA ;
ALIN, K ;
LUBAN, J ;
BEGEMANN, M ;
CRABTREE, GR ;
GOFF, SP .
CELL, 1994, 79 (01) :119-130
[10]   Cochlear outer hair cells undergo an apical circumference remodeling constrained by the hair bundle shape [J].
Etournay, Raphael ;
Lepelletier, Lea ;
de Monvel, Jacques Boutet ;
Michel, Vincent ;
Cayet, Nadege ;
Leibovici, Michel ;
Weil, Dominique ;
Foucher, Isabelle ;
Hardelin, Jean-Pierre ;
Petit, Christine .
DEVELOPMENT, 2010, 137 (08) :1373-1383