Alain Dabdoub, Ph.D.

The Research

University of California San Diego

Canonical wnt signaling in the developing organ of corti

Within the organ of Corti, a single row of inner hair cells and three rows of outer hair cells extend along the basal- to-apical axis of the cochlea. Every sensory hair cell is separated from the next by an intervening non- sensory supporting cell, resulting in an invariant and alternating mosaic. The importance of the formation of this structure is illustrated by the significant auditory deficits in animals with patterning defects in the cochlear duct. Since the perception of sound is based on the integrity and function of this strict cellular organization, it is important to elucidate the developmental processes responsible for generating and regulating this pattern. The development of the cochlea and the organ of Corti requires several events including growth, specification of cell fates, proliferation and differentiation. In many systems the Wnt/_-catenin pathway plays a crucial role in determining cell fate, growth and proliferation. We have data indicating that several Wnt signaling genes are expressed in the cochlea. Furthermore, our preliminary results demonstrate that activating the Wnt/_-catenin pathway in whole organ cochlear explant cultures results in a robust increase in the size of the prosensory domain that gives rise to the organ of Corti and increases in auditory hair cells.