| Thyroid hormone signaling is essential for the maturation and survival of cochlear root cells in mice |
| 論文作者 |
Ma, XH; Jiang, F; Wei, CC; Han, S; Zhang, YQ; Sun, LH; Qu, JX; Ying, H; Chen, YX; Tang, J; He, DZ; Zhang, WPJ; Xie, ZF |
| 期刊/會(huì)議名稱 |
HEARING RESEARCH |
| 論文年度 |
2025 |
| 論文類別 |
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| 摘要 |
Thyroid hormone and its receptors (TRs) are crucial for late-stage cochlear development and the maintenance of endocochlear potential (EP), yet the mechanisms underlying EP reduction in their absence remain unclear. Cochlear outer sulcus root cells undergo significant morphological changes during late-stage development and are thought to play a role in maintaining endolymph homeostasis and EP. Nevertheless, it remains unknown whether thyroid hormone and TRs are essential for root cell differentiation and function. Here, we demonstrate that thyroid hormone or TRs are indispensable for postnatal root cell development and survival in the mouse cochlea. Thyroid hormone deficiency markedly delays root cell differentiation. Otocyst-selective deletion of both Thra and Thrb, but not Thrb alone, leads to a similar impairment, accompanied by early degeneration of root cells, with the stria vascularis unaffected. Furthermore, conditional double knockout of TRs results in a 22 % reduction in mean EP magnitude at 4 months, less severe than the effects observed in global TRs knockout models. Transcriptome analysis reveals that thyroid hormone deficiency downregulates a significant portion of root cell-enriched genes. These findings underscore the redundant roles of TR alpha and TR(3 in promoting the late- stage differentiation and survival of root cells. Additionally, they suggest that the expression of TRs in cochlear epithelium is crucial for maintaining an optimal EP magnitude, while TRs expressed in areas outside cochlear epithelium, particularly in spiral ligament fibrocytes, may also significantly contribute to EP maintenance. This study advances our understanding of thyroid hormone in cochlear outer sulcus development and EP maintenance. |
| 卷 |
459 |
| 影響因子 |
2.5 |
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