Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea

被引:278
作者
Dabdoub, Alain [1 ]
Puligilla, Chandrakala [1 ]
Jones, Jennifer M. [1 ]
Fritzsch, Bernd [2 ]
Cheah, Kathryn S. E. [3 ,4 ]
Pevny, Larysa H. [5 ]
Kelley, Matthew W. [1 ]
机构
[1] NIDCD, Sect Dev Neurosci, NIH, Bethesda, MD 20892 USA
[2] Univ Iowa, Dept Biol Sci, Iowa City, IA 52242 USA
[3] Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China
[4] Univ Hong Kong, Ctr Reprod Dev & Growth, Hong Kong, Hong Kong, Peoples R China
[5] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA
基金
美国国家卫生研究院;
关键词
development; organ of Corti; inner ear; HMG box; bHLH;
D O I
10.1073/pnas.0808175105
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
Sox2 is a high-mobility transcription factor that is one of the earliest markers of developing inner ear prosensory domains. In humans, mutations in SOX2 cause sensorineural hearing loss and a loss of function study in mice showed that Sox2 is required for prosensory formation in the cochlea. However, the specific roles of Sox2 have not been determined. Here we illustrate a dynamic role of Sox2 as an early permissive factor in prosensory domain formation followed by a mutually antagonistic relationship with Atoh1, a bHLH protein necessary for hair cell development. We demonstrate that decreased levels of Sox2 result in precocious hair cell differentiation and an over production of inner hair cells and that these effects are likely mediated through an antagonistic interaction between Sox2 and the bHLH molecule Atoh1. Using gain- and loss-of-function experiments we provide evidence for the molecular pathway responsible for the formation of the cochlear prosensory domain. Sox2 expression is promoted by Notch signaling and Prox1, a homeobox transcription factor, is a downstream target of Sox2. These results demonstrate crucial and diverse roles for Sox2 in the development, specification, and maintenance of sensory cells within the cochlea.
引用
收藏
页码:18396 / 18401
页数:6
相关论文
共 27 条
[1]   Modulation of the activity of multiple transcriptional activation domains by the DNA binding domains mediates the synergistic action of Sox2 and Oct-3 on the Fibroblast growth factor-4 enhancer [J].
Ambrosetti, DC ;
Schöler, HR ;
Dailey, L ;
Basilico, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (30) :23387-23397
[2]   THE MOUSE SNELLS WALTZER DEAFNESS GENE ENCODES AN UNCONVENTIONAL MYOSIN REQUIRED FOR STRUCTURAL INTEGRITY OF INNER-EAR HAIR-CELLS [J].
AVRAHAM, KB ;
HASSON, T ;
STEEL, KP ;
KINGSLEY, DM ;
RUSSELL, LB ;
MOOSEKER, MS ;
COPELAND, NG ;
JENKINS, NA .
NATURE GENETICS, 1995, 11 (04) :369-375
[3]   Role of Sox2 in the development of the mouse neocortex [J].
Bani-Yaghoub, Mahmud ;
Tremblay, Roger G. ;
Lei, Joy X. ;
Zhang, Dongling ;
Zurakowski, Bogdan ;
Sandhu, Jagdeep K. ;
Smith, Brandon ;
Ribecco-Lutkiewicz, Maria ;
Kennedy, Jessica ;
Walker, P. Roy ;
Sikorska, Marianna .
DEVELOPMENTAL BIOLOGY, 2006, 295 (01) :52-66
[4]   Math1:: An essential gene for the generation of inner ear hair cells [J].
Bermingham, NA ;
Hassan, BA ;
Price, SD ;
Vollrath, MA ;
Ben-Arie, N ;
Eatock, RA ;
Bellen, HJ ;
Lysakowski, A ;
Zoghbi, HY .
SCIENCE, 1999, 284 (5421) :1837-1841
[5]   Expression of Prox1 during mouse cochlear development [J].
Bermingham-McDonogh, O ;
Oesterle, EC ;
Stone, JS ;
Hume, CR ;
Huynh, HM ;
Hayashi, T .
JOURNAL OF COMPARATIVE NEUROLOGY, 2006, 496 (02) :172-186
[6]   Vertebrate neurogenesis is counteracted by Sox1-3 activity [J].
Bylund, M ;
Andersson, E ;
Novitch, BG ;
Muhr, J .
NATURE NEUROSCIENCE, 2003, 6 (11) :1162-1168
[7]  
Chen P, 1999, DEVELOPMENT, V126, P1581
[8]   Wnt signaling mediates reorientation of outer hair cell stereociliary bundles in the mammalian cochlea [J].
Dabdoub, A ;
Donohue, MJ ;
Brennan, A ;
Wolf, V ;
Montcouquiol, M ;
Sassoon, DA ;
Hseih, JC ;
Rubin, JS ;
Salinas, PC ;
Kelley, MW .
DEVELOPMENT, 2003, 130 (11) :2375-2384
[9]  
Dailey L, 2001, J CELL PHYSIOL, V186, P315, DOI 10.1002/1097-4652(2001)9999:9999<000::AID-JCP1046>3.0.CO
[10]  
2-Y