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Chicago - Areas of Research:
- Cell Biology, Hearing Sciences, Molecular Neuroscience
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Donna Whitlon, PhD
Mechanisms of neural development and regeneration in the mammalian cochlea
We are studying biochemical mechanisms which underlie neural pathfinding and target selection the mouse cochlea. The mouse cochlea has several characteristics which make it an excellent subject for studies of mammalian neural development.>
- The anatomy of neural development has been well-studied;
- The spiral ganglion neurons lie close to their peripheral targets, making it possible to observe entire fiber pathways in one piece of tissue;
- Deaf mouse mutants with defects in the cochlea are available for comparative studies; and
- the mouse cochlea can be maintained in organ culture, where the nerve fibers make connections with the hair cell targets in a manner similar to that observed in vivo.
In other areas of the nervous system, cell surface and extracellular matrix molecules, known as adhesion molecules, have been implicated in mechanisms of neural growth, pathfinding, target selection and synaptogenesis. In the cochlea, we have mapped the adhesion molecules NCAM, L1, E-cadherin, tenascin, thrombospondin, PSA and syndecan-1 to nerve fibers, to surfaces along the neural growth paths, and/or to the hair cell targets during development. Our map demonstrates regional and zonal differences in the constitution of adhesion molecules. These differences reflect potential variations in the interactions between nerve fibers and their environments, variations which have the potential to guide neurite growth. Using the in vitro organ culture system, we are using perturbation experiments (in which the functions of specific molecules are blocked immunologically) to explore the roles played by specific adhesion molecules. Taken together with studies on the growth capabilities and preferences of different classes of spiral ganglion neurons in ganglion explant culture and the growth of nerve fibers in transgenic "null" mutant mice, these experiments will give insight into the functional roles of adhesion molecules during development in this mammalian system. The methods used in these studies are: immunocytochemistry, in situ hybridization, basic DNA cloning techniques, organ culture, and microscopy.

