Knockdown of Foxg1 in Sox9+ supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse utricle

• Published in: Aging (Albany, NY.) NY.), 2020-10, Vol.12 (20), p.19834-19851
• Main Authors: Zhang, Yuan, Zhang, Shasha, Zhang, Zhonghong, Dong, Ying, Ma, Xiangyu, Qiang, Ruiying, Chen, Yin, Gao, Xia, Zhao, Chunjie, Chen, Fangyi, He, Shuangba, Chai, Renjie
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Cell Lineage; Cell Proliferation; Cell Transdifferentiation; Female; Forkhead Transcription Factors - deficiency; Forkhead Transcription Factors - genetics; Gene Expression Regulation, Developmental; Hair Cells, Auditory - drug effects; Hair Cells, Auditory - metabolism; Hair Cells, Auditory - pathology; Labyrinth Supporting Cells - drug effects; Labyrinth Supporting Cells - metabolism; Labyrinth Supporting Cells - pathology; Male; Mice, Knockout; Neomycin - toxicity; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Ototoxicity; Phenotype; Priority Research Paper; Saccule and Utricle - drug effects; Saccule and Utricle - metabolism; Saccule and Utricle - pathology; Signal Transduction; SOX9 Transcription Factor - genetics; SOX9 Transcription Factor - metabolism
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.104009

Foxg1 plays important roles in regeneration of hair cell (HC) in the cochlea of neonatal mouse. Here, we used Sox9-CreER to knock down in supporting cells (SCs) in the utricle in order to investigate the role of Foxg1 in HC regeneration in the utricle. We found Sox9 an ideal marker of utricle SCs and bred Sox9 Foxg1 mice to conditionally knock down in utricular SCs. Conditional knockdown (cKD) of in SCs at postnatal day one (P01) led to increased number of HCs at P08. These regenerated HCs had normal characteristics, and could survive to at least P30. Lineage tracing showed that a significant portion of newly regenerated HCs originated from SCs in cKD mice compared to the mice subjected to the same treatment, which suggested SCs trans-differentiate into HCs in the cKD mouse utricle. After neomycin treatment , more HCs were observed in cKD mice utricle compared to the control group. Together, these results suggest that cKD in utricular SCs may promote HC regeneration by inducing trans-differentiation of SCs. This research therefore provides theoretical basis for the effects of Foxg1 in trans-differentiation of SCs and regeneration of HCs in the mouse utricle.