1. Involvement of Dmp1 in the Precise Regulation of Hair Bundle Formation in the Developing Cochlea
- Author
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Yanmei Wang, Jihan Lyu, Xiaoqing Qian, Binjun Chen, Haojie Sun, Wenwei Luo, Fanglu Chi, Hongzhe Li, and Dongdong Ren
- Subjects
Dmp1 ,inner ear development ,cell-intrinsic polarity ,stereocilia morphology ,kinocilium positioning ,General Immunology and Microbiology ,General Agricultural and Biological Sciences ,General Biochemistry, Genetics and Molecular Biology - Abstract
Dentin matrix protein 1 (Dmp1) is a highly phosphorylated, extracellular matrix protein that is extensively expressed in bone and teeth but also found in soft tissues, including brain and muscle. However, the functions of Dmp1 in the mice cochlea are unknown. Our study showed that Dmp1 was expressed in auditory hair cells (HCs), with the role of Dmp1 in those cells identified using Dmp1 cKD mice. Immunostaining and scanning electron microscopy of the cochlea at P1 revealed that Dmp1 deficiency in mice resulted in an abnormal stereociliary bundle morphology and the mispositioning of the kinocilium. The following experiments further demonstrated that the cell-intrinsic polarity of HCs was affected without apparent effect on the tissue planer polarity, based on the observation that the asymmetric distribution of Vangl2 was unchanged whereas the Gαi3 expression domain was enlarged and Par6b expression was slightly altered. Then, the possible molecular mechanisms of Dmp1 involvement in inner ear development were explored via RNA-seq analysis. The study suggested that the Fgf23–Klotho endocrine axis may play a novel role in the inner ear and Dmp1 may regulate the kinocilium–stereocilia interaction via Fgf23–Klotho signaling. Together, our results proved the critical role of Dmp1 in the precise regulation of hair bundle morphogenesis in the early development of HCs.
- Published
- 2023