The effect of Stathmin-1 on regeneration of hair cells in Cochlea, Utricle and Saccule via transdifferentiation of supporting cells

Hair cells of the Corti organ are highly sensitive to external damage and are not regenerative in humans and mammals, but there is hope to enable regeneration in the future by activating certain signaling pathways. A key molecule of hair cell regeneration is p27^KIP1. This cell cycle-regulating protein is expressed in mammals after hearing development in the hair cells and prevents later proliferation. However, the signaling pathways by which p27<sup>KIP1</sup > inhibits hair cell regeneration are still unknown. STATHMIN,a microtubule-interacting molecule, could be a molecule that could be involved in regeneration. P27<sup>KIP1</sup > has a proven cell cycle inhibiting interaction with STATHMIN. In preliminary experiments of the working group, STATHMIN could be detected in cochlear support cells, whose expression pattern followed the maturity of hearing and persisted into old age. Based on this, whole-mount Corti organs of mice are cultivated on day p3 to p6 after damage by an aminoglycoside with corresponding STATHMIN-modulators such as forskolin and VIP in order to analyze effects on the transdifferentiation of the supporting cells after immunohistochemical staining. A precise observation of the conversion from support to hair cells is carried out by Live Cell Imaging. In addition, the expression pattern of STATHMIN, its phosphorylated isoforms and its interaction molecules p27<sup>KIP1</sup > and Sox-2 are presented using cryocut preparations. With the help of the proliferation marker BrdU, it was found that the phosphorylation of stathmin-1 leads to the proliferation of cochlear support cells and has an effect on transdifferentiation into new hair cells. The same effect could be observed for utricle and saccule.

Conflict of Interest

The author declares that there is no conflict of interest.

Publication History

Article published online:
24 May 2022