A limited understanding of cochlear biochemistry has hindered attempts to unravel the biochemical mechanisms directing neuron/hair cell connections. In other tissues, cell adhesion molecules have been implicated in the molecular mechanisms underlying directed axonal growth, fasciculation, intercell recognition and synaptogenesis. Previous work has demonstrated the presence of the cell adhesion molecules N-CAM and L1 in the inner ear. The proposed study asks: What are the roles of N-CAM and L1 in neuronal development in the cochlear? The hypothesis is that the cell adhesion molecules facilitate directed axonal growth and assist in the establishment of correct neuron/hair cell connections in the cochlea.. The developing cochlea from the intact mouse (a preparation with both afferent and efferent connections) and from tissue culture (a purely afferent preparation) will be used in this study. In addition,k two mouse models with impaired neurosensory connections will be studied (the Bronx Waltzer mutant and an experimentally produced hyperthyroid animal). The project aims to identify and attempt to quantitate cell adhesion molecules and their molecular forms in developing cochlea by Western Blot and ELISA analyses; to visualize cell adhesion molecules in developing tissue by immunocytochemistry at the light and electron microscope levels in order to compare their distributions to the known temporospatial development of the cochlear innervation; and to deduce the role of the molecules in vitro with antibody perturbation studies Successful experiments can be expected to 1) identify cell adhesion proteins that may participate in the development of defined morphological arrangements in the cochlea and 2) provide information on their roles in the development. This work is pertinent to the study of the biochemistry of deafness caused by impaired cochlear development.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DC000653-05
Application #
2125878
Study Section
Hearing Research Study Section (HAR)
Project Start
1990-05-01
Project End
1995-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Pediatrics
Type
Other Domestic Higher Education
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Zheng, Lili; Zheng, Jing; Whitlon, Donna S et al. (2010) Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model. J Neurosci 30:7187-201
Whitlon, D S; Tieu, D; Grover, M et al. (2009) Spontaneous association of glial cells with regrowing neurites in mixed cultures of dissociated spiral ganglia. Neuroscience 161:227-35
Whitlon, D S; Zhang, X (1997) Polysialic acid in the cochlea of the developing mouse. Int J Dev Neurosci 15:657-69
Whitlon, D S; Gabel, C; Zhang, X (1996) Cochlear inner hair cells exist transiently in the fetal Bronx Waltzer (bv/bv) mouse. J Comp Neurol 364:515-522
Wickesberg, R E; Whitlon, D; Oertel, D (1994) In vitro modulation of somatic glycine-like immunoreactivity in presumed glycinergic neurons. J Comp Neurol 339:311-27
Whitlon, D S (1993) E-cadherin in the mature and developing organ of Corti of the mouse. J Neurocytol 22:1030-8
Whitlon, D S; Sobkowicz, H M (1991) Patterns of hair cell survival and innervation in the cochlea of the bronx waltzer mouse. J Neurocytol 20:886-901