Precise targeting of afferent auditory projections is critical for hearing yet the molecular cues which guide axonal path finding in the developing cochlea are not well understood. In other developing systems, the slit/robo signaling pathway provides critical guidance to both axonal and dendritic processes. Members of this pathway are expressed in the mammalian inner ear during the period of neurite outgrowth but their function in the cochlea is not known. The objective of the proposed research is to determine whether slit and robo serve as guidance cues for auditory neuritis.
The specific aims are: 1.) To determine the temporo-spatial expression pattern of slit and robo in the developing cochlea; 2.) To determine the effect of exogenous slit on neurite outgrowth in spiral ganglion neurons 3.) To determine whether deletion of slit genes results in misguidance of auditory axons. The identification of molecules involved in axonal path finding in the developing cochlea may impact the clinical treatment of sensorineural haring loss. These molecules could potentially be coupled to a cochlear implant to promote contact between afferent dendrites and the device. Additionally, as progress is made in the area of hair cell regeneration, improved understanding the axonal guidance factors will prove vital for building connections between these new elements and the central nervous system. ? ? The candidate is a neurotologist with a research background in auditory development. Her career goal is to integrate advances in inner ear development into novel therapeutic interventions for hearing loss. Her institution is committed to this goal and has provided the necessary space, protected time, and resources. She has put together a team of mentors who can not only provide extensive scientific guidance, but also foster her development as an independent investigator. ? ?
| Billig, I; Yeager, M S; Blikas, A et al. (2007) Neurons in the cochlear nuclei controlling the tensor tympani muscle in the rat: a study using pseudorabies virus. Brain Res 1154:124-36 |
