Wnt signaling during cochlear development

• Wnt activation stimulates proliferation during early prosensory formation.
• Fgf20-mediated Sox2 elevation could be titrated by Wnt signaling.
• High Sox2 levels block neural formation via Notch and force non-neuronal fates.
• Wnts can reprogram support cells to proliferate and differentiate into hair cells.
• Wnts regulate hair cell bundle orientation and convergent extension in the cochlea.

Wnt signaling is a hallmark of all embryonic development with multiple roles at multiple developmental time points. Wnt signaling is also important in the development of several organs, one of which is the inner ear, where it participates in otic specification, the formation of vestibular structures, and the development of the cochlea. In particular, we focus on Wnt signaling in the auditory organ, the cochlea. Attempting to dissect the multiple Wnt signaling pathways in the mammalian cochlea is a challenging task due to limited expression data, particularly at proliferating stages. To offer predictions about Wnt activity, we compare cochlear development with that of other biological systems such as Xenopus retina, brain, cancer cells and osteoblasts. Wnts are likely to regulate development through crosstalk with other signaling pathways, particularly Notch and FGF, leading to changes in the expression of Sox2 and proneural (pro-hair cell) genes. In this review we have consolidated the known signaling pathways in the cochlea with known developmental roles of Wnts from other systems to generate a potential timeline of cochlear development.