The acquisition of positional information in the developing cochlea

Abstract

The sensory epithelium of the mammalian murine auditory organ, the organ of Corti, is an exquisite example of how specialized asymmetry dictates auditory function. Across the radial axis, the organ consists of three rows of outer hair cells to one row of inner hair cells, which are innervated by efferent and afferent neurons. The mechanosensory inner hair cells that reside in the neural compartment detect sound whereas the outer hair cells in the abneural compartment modulate sound levels. A complex combination of spatio‐temporal signaling inputs across the radial axis endows cells with positional information to take on specific cell fates.The Wnt and Bmp pathways are two potential signaling mechanisms that influence this radial asymmetry in an opposing manner. We analyzed the requirement of the Bmp pathway for setting up cochlear patterning. Smad4 cKOs showed a loss of the abneural compartment. Prolonged Bmp inhibition decreased the formation of the abneural compartment and outer hair cells. Bmp was required for determining the abneural boundary of the sensory domain. Immediately after hair cell differentiation, Bmp signaling was no longer required. Bmp is necessary, but not sufficient for patterning the entire epithelium. Activation of the Wnt pathway leads to a selective expansion of the neural compartment and inner hair cells. This selective neural expansion was also conserved in the chicken cochlea. Signaling crosstalk of these pathways in a spatiotemporal manner is necessary for proper patterning of the organ of Corti.Support or Funding Information R21DC016376R01DC002756R01GM132501