Increased Type i and Decreased Type Ii Hair Cells after Deletion of Sox2 in the Developing Mouse Utricle
Lu, J.; Hu, L.; Ye, B.; Hu, H.; Tao, Y.; Shu, Y.; Hao Chiang; Borse, V.; Xiang, M.; Wu, H.; Edge, A.S.B.; Shi, F.
Neuroscience 422: 146-160
2019
ISSN/ISBN: 1873-7544
PMID: 31678344
DOI: 10.1016/j.neuroscience.2019.09.027
Accession: 069475146
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 Sox2flox 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.