The chromatin remodeler Brg1 is essential for cochlear sensory epithelium differentiation and patterning

被引：0

作者：

Song, Yuning ^{[1
]}

Dou, Zhilin ^{[2
]}

Liu, Wenwen ^{[3
]}

Zhang, Aizhen ^{[3
]}

Gao, Xiaotong ^{[1
]}

Shi, Hongbiao ^{[2
]}

Zhang, Zhixiong ^{[2
]}

Gao, Jiangang ^{[1
]}

Jin, Yecheng ^{[2
]}

机构：

[1] Shandong Univ, Sch Life Sci, Shandong Prov Key Lab Anim Cell & Dev Biol, 27 Shanda Nanlu, Jinan 250100, Peoples R China

[2] Shandong Univ, Cheeloo Coll Med, Sch Basic Med Sci, Key Lab Expt Teratol,Minist Educ,Dept Med Genet, 44 Wenhua Xilu, Jinan 250012, Peoples R China

[3] Shandong Univ, Shandong Prov ENT Hosp, Dept Otolaryngol Head & Neck Surg, Jinan 250022, Peoples R China

来源：

HUMAN MOLECULAR GENETICS | 2025年

基金：

中国国家自然科学基金;

关键词：

hair cell; organ of Corti; BAF complex; hearing loss; development; HAIR CELL-DIFFERENTIATION; COFFIN-SIRIS SYNDROME; SONIC HEDGEHOG; TISSUE REGENERATION; PROGENITOR CELLS; CYCLE EXIT; DUAL ROLE; ORGAN; COMPLEX; SOX2;

D O I：

10.1093/hmg/ddaf019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Human genome analyses have revealed that abnormal BAF (BRG1/BRM-associated factor) complex is highly associated with hearing loss. However, the underlying pathogenesis remains largely unknown. Disrupted structure and function of the organ of Corti is the most prevalent cause of sensorineural hearing loss in mammals. Here, we investigated the role of Brg1-based BAF complex during the differentiation and development of the auditory sensory epithelium, a crucial period for the formation of the organ of Corti. Our findings indicate that deletion of Brg1 leads to premature hair cell (HC) differentiation by inactivating Sonic hedgehog (Shh) signaling. Despite the formation of HCs, subsequent differentiation of inner hair cells (IHCs) and outer hair cells (OHCs) was impaired. Additionally, we observed that the mosaic-like arrangement of HCs and supporting cells (SCs) was disrupted resulting in abnormal sensory epithelium patterning. Furthermore, we found the planar cell polarity of the Brg1-deficient cochlea was abnormal. Our study demonstrates the pivotal role of Brg1 in the differentiation and patterning of the organ of Corti.

引用

页数：16

共 69 条

[21] Advances in gene therapy hold promise for treating hereditary hearing loss [J].