Notch-Wnt-Bmp crosstalk regulates radial patterning in the mouse cochlea in a spatiotemporal manner.

The sensory cells of the mammalian organ of Corti assume a precise mosaic arrangement during embryonic development. Manipulation of Wnt signaling can modulate the proliferation of cochlear progenitors, but whether Wnts are responsible for patterning compartments, or specific hair cells within them, is unclear. To address how the precise timing of Wnt signaling impacts patterning across the radial axis, mouse cochlear cultures were initiated at embryonic day 12.5 and subjected to pharmacological treatments at different stages. Early changes in major patterning genes were assessed to understand the mechanisms underlying alterations of compartments. Results show that Wnt activation can promote medial cell fates by regulating medially expressed Notch genes in a spatiotemporal manner. Wnts can also suppress lateral cell fates by antagonizing Bmp4 expression. Perturbation of the Notch and Bmp pathways revealed which secondary effects were linked to these pathways. Importantly, these effects on cochlear development are dependent on the timing of drug delivery. In conclusion, Wnt signaling in the cochlea influences patterning through complex crosstalk with the Notch and Bmp pathways at several stages of embryonic development.