Inactivation of STAT3 Signaling Impairs Hair Cell Differentiation in the Developing Mouse Cochlea

Summary Although STAT3 signaling is demonstrated to regulate sensory cell differentiation and regeneration in the zebrafish, its exact role is still unclear in mammalian cochleae. Here, we report that STAT3 and its activated form are specifically expressed in hair cells during mouse cochlear development. Importantly, conditional cochlear deletion of Stat3 leads to an inhibition on hair cell differentiation in mice in vivo and in vitro. By cell fate analysis, inactivation of STAT3 signaling shifts the cell division modes from asymmetric to symmetric divisions from supporting cells. Moreover, inhibition of Notch signaling stimulates STAT3 phosphorylation, and inactivation of STAT3 signaling attenuates production of supernumerary hair cells induced by a Notch pathway inhibitor. Our findings highlight an important role of the STAT3 signaling during mouse cochlear hair cell differentiation and may have clinical implications for the recovery of hair cell loss-induced hearing impairment.
Highlights • STAT3 signaling is activated during hair cell development and regeneration • Inactivation of STAT3 signaling inhibits hair cell differentiation in vivo and in vitro • STAT3 signaling regulates symmetric and asymmetric cell division modes • STAT3 partially mediates Notch signaling-controlled hair cell production
The mechanism of mammalian hair cell development is not fully understood. In this article, Wei-Qiang Gao and colleagues show that inactivation of STAT3 signaling impairs mammalian cochlear hair cell differentiation, by influencing asymmetric and symmetric cell division modes. The STAT3 pathway is downstream of the Notch signaling for the regulation of hair cell production.