PROX1 Controls Cellular Patterning, Innervation and Differentiation in the Mouse Organ of Corti

Abstract

The organ of Corti is divided into functional compartments responsible for hearing or cochlear amplification. A medial compartment containing inner hair cells innervated by Type I spiral ganglion neurons and a lateral compartment containing outer hair cells innervated by Type II spiral ganglion neurons. Supporting cells also differ, with lateral compartment pillar cells and Deiters cells developing specialized cellular structures to support outer hair cell electromotility. We bred organ of Corti-restricted Prox1 conditional knockout mice to study lateral compartment development because PROX1 is the first transcription factor expressed strictly in lateral compartment supporting cells. In the absence of Prox1, supporting cell numbers increased without corresponding changes in outer hair cells, and they appear incompletely differentiated based on morphological criteria. Outer hair cell number was not impacted but innervation was disrupted with many afferent neurons turning incorrectly towards the cochlear apex. RNAseq revealed no changes in gene expression that could account for the innervation phenotype. Therefore, we propose that PROX1 promotes pillar and Deiters cell differentiation and organization that has secondary effects on innervation but is not required for compartment specification.