The Journal of Neuroscience, April 1, 2002, 22(7):2607-2616
Cell Density and N-Cadherin Interactions Regulate Cell
Proliferation in the Sensory Epithelia of the Inner Ear
Mark E.
Warchol
Fay and Carl Simons Center for Biology of Hearing and
Deafness, Central Institute for the Deaf, and Departments of
Otolaryngology and Anatomy and Neurobiology, Washington University
School of Medicine, St. Louis, Missouri 63110-1549
Sensory hair cells in the inner ears of nonmammalian vertebrates
can regenerate after injury. In many species, replacement hair cells
are produced by the proliferation of epithelial supporting cells. Thus,
the ability of supporting cells to undergo renewed proliferation is a
key determinant of regenerative ability. The present study used
cultures of isolated inner ear sensory epithelia to identify cellular
signals that regulate supporting cell proliferation. Small pieces of
sensory epithelia from the chicken utricle were cultured in glass
microwells. Under those conditions, cell proliferation was inversely
related to local cell density. The signaling molecules N-cadherin,
-catenin, and focal adhesion kinase were immunolocalized in the
cultured epithelial cells, and high levels of phosphotyrosine immunoreactivity were present at cell-cell junctions and focal contacts of proliferating cells. Binding of microbeads coated with a
function-blocking antibody to N-cadherin inhibited ongoing proliferation. The growth of epithelial cells was also affected by the
density of extracellular matrix molecules. The results suggest that
cell density, cell-cell contact, and the composition of the
extracellular matrix may be critical influences on the regulation of
sensory regeneration in the inner ear.
Key words:
auditory; vestibular; regeneration; hair cell; adhesion
molecules; cell culture
Copyright © 2002 Society for Neuroscience 0270-6474/02/2272607-10$05.00/0
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