Cell density and N-cadherin interactions regulate cell proliferation in the sensory epithelia of the inner ear.
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, beta-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.
Warchol
Mark E
ME
Fay and Carl Simons Center for Biology of Hearing and Deafness, Central Institute for the Deaf, and Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri 63110-1549, USA. mwarchol@cid.wustl.edu
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002645:Chickens; D046508:Culture Techniques; D003598:Cytoskeletal Proteins / Q000378:metabolism; D007758:Ear, Inner / Q000166:cytology* / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D015534:Trans-Activators; D014212:Tretinoin / Q000494:pharmacology; D051176:beta Catenin
D000906:Antibodies; D015820:Cadherins; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D007797:Laminin; D015534:Trans-Activators; D051176:beta Catenin; D019000:Phosphotyrosine; D014212:Tretinoin; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases