The sensory cells of the inner ear, hair cells, provide vertebrates with the ability
to detect auditory stimuli and balance. In mammals, cochlear hair cells, those
responsible for hearing, do not regenerate. Zebrafish hair cells do regenerate. Gaining
an understanding of the role and regulation of the genes involved in the formation and
regeneration of these cells may provide information important for the development of
genetic therapies.
We show that zebrafish atoh1 acts as the proneural gene responsible for defining
the equivalence group from which hair cells form. Expression of atoh1 is dependent
upon Fgf and Pax. Atoh1 induces expression of delta, resulting in activation of Notch
and subsequent lateral inhibition. Another factor known to be important for hair cell
formation in mice is Sox2. In zebrafish, sox2 expression is downstream of Atoh1, Notch
and Fgf. Zebrafish Sox2 is not required for hair cell formation, but rather Sox2 is
important for hair cell maintenance.
In zebrafish, otic hair cell regeneration has not yet been characterized. We show
that, following laser ablation, hair cells regenerate by way of transdifferentiation. We further show that this regeneration requires Sox2 activity. These data suggest that Sox2
acts to maintain support cell plasticity. This role is likely conserved because Sox2 is
also important for stem cell plasticity in mammals. This new understanding of the role
and regulation of both Atoh1 and Sox2 provides essential information that can be used to
further efforts to provide genetic therapies for hair cell regeneration in mammals.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2010-08-8300 |
| Date | 2010 August 1900 |
| Creators | Millimaki, Bonny Butler |
| Contributors | Riley, Bruce B. |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | application/pdf |
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