Increased Type I and Decreased Type II Hair Cells after Deletion of Sox2 in the Developing Mouse Utricle

Jingrong Lu; Lingxiang Hu; Bin Ye; Haixia Hu; Yong Tao; Yilai Shu; Hao Chiang; Vikrant Borse; Mingliang Xiang; Hao Wu; Albert S B Edge; Fuxin Shi

doi:10.1016/j.neuroscience.2019.09.027

Increased Type I and Decreased Type II Hair Cells after Deletion of Sox2 in the Developing Mouse Utricle

Neuroscience. 2019 Dec 1:422:146-160. doi: 10.1016/j.neuroscience.2019.09.027. Epub 2019 Oct 31.

Authors

Jingrong Lu¹, Lingxiang Hu², Bin Ye¹, Haixia Hu¹, Yong Tao², Yilai Shu³, Hao Chiang⁴, Vikrant Borse⁴, Mingliang Xiang¹, Hao Wu⁵, Albert S B Edge⁴, Fuxin Shi⁶

Affiliations

¹ Department of Otolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, China.
² Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, China; Department of Otolaryngology Head & Neck Surgery, Shanghai 9th People's Hospital/Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
³ ENT Institute and Otorhinolaryngology Department, Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China; Key Laboratory of Hearing Medicine of National Health and Family Planning Commission (NHFPC), Shanghai, China.
⁴ Department of Otolaryngology, Harvard Medical School, Boston, MA 02115, USA; Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, MA 02114, USA.
⁵ Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, China; Department of Otolaryngology Head & Neck Surgery, Shanghai 9th People's Hospital/Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Electronic address: wuhao622@sina.cn.
⁶ Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Decibel Therapeutics, Boston, MA 02215, USA. Electronic address: fshi@decibeltx.com.

Abstract

The vestibular system of the inner ear contains Type I and Type II hair cells (HCs) generated from sensory progenitor cells; however, little is known about how the HC subtypes are formed. Sox2 (encoding SRY-box 2) is expressed in Type II, but not in Type I, HCs. The present study aimed to investigate the role of SOX2 in cell fate determination in Type I vs. Type II HCs. First, we confirmed that Type I HCs developed from Sox2-expressing cells through lineage tracing of Sox2-positive cells using a CAG-tdTomato reporter mouse crossed with a Sox2-CreER mouse. Then, Sox2 loss of function was induced in HCs, using Sox2^flox transgenic mice crossed with a Gfi1-Cre driver mouse. Knockout of Sox2 in HCs increased the number of Type I HCs and decreased the number of Type II HCs, while the total number of HCs and Sox2-positive supporting cells did not change. In addition, the effect of Sox2-knockout persisted into adulthood, resulting in an increased number of Type I HCs. These results demonstrate that SOX2 plays a critical role in the determination of Type II vs. Type I HC fate. The results suggested that Sox2 is a potential target for generating Type I HCs, which may be important for regenerative strategies for balance disorders.

Keywords: SOX2; balance disorder; hair cell; utricle; vestibule.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / physiology*
Animals
Cell Count
Cell Differentiation / physiology*
Cell Lineage / physiology
Hair Cells, Vestibular / physiology*
Mice
Mice, Knockout
Mice, Transgenic
SOXB1 Transcription Factors / genetics
SOXB1 Transcription Factors / physiology*
Saccule and Utricle / cytology

Substances

SOXB1 Transcription Factors
Sox2 protein, mouse

Grants and funding

R01 DC014089/DC/NIDCD NIH HHS/United States