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Volume 16, Number 17,
Issue of September 1, 1996
pp. 5466-5477
Copyright ©1996 Society for Neuroscience
Regenerative Proliferation in Organ Cultures of the Avian
Cochlea: Identification of the Initial Progenitors and Determination of
the Latency of the Proliferative Response
Received Jan. 18, 1996; revised May 31, 1996; accepted June 5, 1996.
Mark E. Warchol1 and
Jeffrey T. Corwin1, 2
1 Departments of Otolaryngology-Head and Neck Surgery
and 2 Neuroscience, School of Medicine, University of
Virginia, Charlottesville, Virginia 22908
Sensory hair cells in the cochleae of birds are regenerated after
the death of preexisting hair cells caused by acoustic overstimulation
or administration of ototoxic drugs. Regeneration involves renewed
proliferation of cells in an epithelium that is otherwise mitotically
quiescent. To determine the identity of the first cells that
proliferate in response to the death of hair cells and to measure the
latency of this proliferative response, we have studied hair-cell
regeneration in organ culture. Cochleae from hatchling chicks were
placed in culture, and hair cells were killed individually by a laser
microbeam. The culture medium was then replaced with a medium that
contained a labeled DNA precursor. The treated cochleae were incubated
in the labeling media for different time periods before being fixed and
processed for the visualization of proliferating cells. The first cells
to initiate DNA replication in response to the death of hair cells were
supporting cells within the cochlear sensory epithelium. All of the
labeled supporting cells were located within 200 µm of the hair-cell
lesions. These cells first entered S-phase ~16 hr after the death of
hair cells. The results indicate that supporting cells are the
precursors of regenerated hair cells and suggest that regenerative
proliferation of supporting cells is triggered by signals that act
locally within the damaged epithelium.
Key words:
hair cell;
hearing;
ear;
regeneration;
cochlea;
auditory system;
precursor
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