Purinergic Signaling Regulates the Form and Function of the Developing Cochlea

Abstract

Hearing depends on a properly formed inner ear to transmit sound information to the brain. Purinergic signaling has been implicated in the development of the inner ear, especially with regard to the cochlea. P2rx3 receptors are predominantly expressed in many afferent sensory neurons and have been shown to play an essential role in afferent signaling transduction. However, the function of this sensory neuron-specific purinergic receptor in auditory development remains elusive. During development, primary auditory neurons, also known as spiral ganglion neurons (SGNs), build connections with sensory hair cells. In the murine cochlea, P2rx3 is highly expressed in embryonic SGNs, suggesting a role of extracellular ATP in regulating their development via P2rx3-mediated calcium signaling. By using P2rx3 null mice combined with powerful techniques including genetic sparse labeling and calcium imaging, I have discovered that P2rx3 receptors regulate SGN maturation. My doctoral dissertation offers new insights into the fundamental principles of extracellular ATP-mediated primary afferent neuron maturation and hearing establishment. This knowledge not only furthers our understanding of neuronal branch development but also empowers therapeutic endeavors toward regenerating SGNs.