Deafness and hearing loss due to damage of the inner ear and cochlear nerve remain as the major incurable otological disorders today, despite recent advances with cochlear prostheses. Less common, but of much concern, are congenital forms of damage, since the resulting hearing impairment profoundly disturbs the development of communication skills. The goal of the present proposal is to elucidate the mechanisms controlling the assembly of the sensorineural structures of the Inner ear and their connections with the central auditory pathways. The approach uses in vitro methods to analyze the role of sensorineural interactions in the development of these auditory structures. Dissociated cell cultures of defined tissue explants from the anlagen of the ear and acoustic nuclei of chicken or quail embryos are used to determine the cell types Involved in these interactions.
The aim i s to identify the specific cell types that interact during neurogenesis of the cochlear ganglion and nucleus and to characterize the cellular Interactions occurring In vitro, whether trophic or tropic, permissive or instructive, whether mediated by contact of diffusible factors. Experiments are designed to reveal factors involved in these interactions and the loci of their actions at the molecular level. Antibodies will be used for localizing such molecules to specific cell types at the critical stages and to perturb the developmental process in situ. Ultimately these findings should provide a rational basis for developing transplantation of neuronal and otic epithelial cells into damaged cochleas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS029613-04
Application #
2267732
Study Section
Hearing Research Study Section (HAR)
Project Start
1991-04-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1996-03-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Anatomy/Cell Biology
Type
Schools of Dentistry
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
Hossain, Waheeda A; Antic, Srdjan D; Yang, Yang et al. (2005) Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea. J Neurosci 25:6857-68
Liesi, Paivi; Akinshola, Emmanuel; Matsuba, Kenji et al. (2003) Cellular migration in the postnatal rat cerebellar cortex: confocal-infrared microscopy and the rapid Golgi method. J Neurosci Res 72:290-302
Bilak, Masako M; Hossain, Waheeda A; Morest, D Kent (2003) Intracellular fibroblast growth factor produces effects different from those of extracellular application on development of avian cochleovestibular ganglion cells in vitro. J Neurosci Res 71:629-47
Hossain, W Amin; Brumwell, C L; Morest, D K (2002) Sequential interactions of fibroblast growth factor-2, brain-derived neurotrophic factor, neurotrophin-3, and their receptors define critical periods in the development of cochlear ganglion cells. Exp Neurol 175:138-51
Zhou, X; Baier, C; Hossain, W A et al. (2001) Expression of a voltage-dependent potassium channel protein (Kv3.1) in the embryonic development of the auditory system. J Neurosci Res 65:24-37
Brumwell, C L; Hossain, W A; Morest, D K et al. (2000) Role for basic fibroblast growth factor (FGF-2) in tyrosine kinase (TrkB) expression in the early development and innervation of the auditory receptor: in vitro and in situ studies. Exp Neurol 162:121-45
Hossain, W A; Morest, D K (2000) Fibroblast growth factors (FGF-1, FGF-2) promote migration and neurite growth of mouse cochlear ganglion cells in vitro: immunohistochemistry and antibody perturbation. J Neurosci Res 62:40-55
Hendriks, R; Morest, D K; Kaczmarek, L K (1999) Shaw-like potassium currents in the auditory rhombencephalon throughout embryogenesis. J Neurosci Res 58:791-804
Hrynkow, S H; Morest, D K; Bilak, M et al. (1998) Multiple roles of neural cell adhesion molecule, neural cell adhesion molecule-polysialic acid, and L1 adhesion molecules during sensory innervation of the otic epithelium in vitro. Neuroscience 87:423-37
Hrynkow, S H; Morest, D K; Brumwell, C et al. (1998) Spatio-temporal diversity in the microenvironments for neural cell adhesion molecule, neural cell adhesion molecule-polysialic acid, and L1-cell adhesion molecule expression by sensory neurons and their targets during cochleo-vestibular innervation. Neuroscience 87:401-22

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