Progenitors influence patterning of the sensory epithelium.

During 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 analyzing Mybl2 loss-of-function cochleas, we show that Mybl2 simultaneously specifies the progenitor niche and the size of the sensory domain, and influences the positioning of the medial sensory domain boundary via Jag1 regulation during the mid-gestational stages. Mybl2 conditional knockout resulted in a decrease of proliferation within the progenitor niche. During the late embryonic stages, conditional knockout of Mybl2 produced a wider sensory epithelium across the radial axis with an increase in ectopic inner hair cell formation. These data suggest that Mybl2-positive progenitors play a role in boundary formation and patterning the sensory epithelium. Summary StatementMybl2 is 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.