Sensory progenitors influence patterning of the mammalian auditory sensory epithelium

Abstract

AbstractDuring embryonic development Wnt signaling has been shown to influence proliferation and sensory formation in the cochlea. How the dual nature of Wnt signaling is coordinated is unknown. In this study, we define a novel role for a Wnt regulated gene,Mybl2,which was already known to be important for proliferation, in influencing patterning and determining the size of the sensory epithelium in the murine cochlea. Using a quantitative spatial analysis approach and analyzingMybl2loss-of-function cochleas, we show thatMybl2simultaneously specifies the progenitor niche and the size of the sensory domain, and influences the positioning of the medial sensory domain boundary viaJag1regulation during the mid-gestational stages.Mybl2conditional knockout resulted in a decrease of proliferation within the progenitor niche. During the late embryonic stages, conditional knockout ofMybl2produced a wider sensory epithelium across the radial axis with an increase in ectopic inner hair cell formation. These data suggest thatMybl2-positive progenitors play a role in boundary formation and patterning the sensory epithelium.Summary StatementMybl2is a Wnt-regulated gene encoding a transcription factor that is expressed in the cochlear progenitor niche and influences the boundary formation between the niche and the sensory domain during mid-cochlear developmental stages, thereby impacting the size of the sensory epithelium.