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University of Helsinki Institute of Biotechnology
Institute of Biotechnology
Inner Ear Development

Ulla Pirvola
Tel. +358-9-191 59591
E-mail: ulla -dot- pirvola
-at- helsinki -dot- fi

Institute of Biotechnology
Street address: Viikinkaari 9 (P.O.Box 56)
00014 University of Helsinki
Tel: +358-9-1911
fax +358-9-1915 9366

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The inner ear – from development to therapeutic applications

The inner ear sensory cells - the hair cells and neurons - are postmitotic, differentiated cells. They are key players in hearing and balance functions. Sensory cell death due to environmental and genetic factors is irreversible, because lost cells are not replaced by new ones. Sensory cell loss leads to functional deficits. More that 300 million people worldwide are affected by hearing impairment. This condition will be an increasing challenge to public health in the future. There are no drugs or other biological interventions available to treat deafness due to sensory cell loss. The development of these therapies is based on advances in basic research on the inner ear.

We study the molecular mechanisms that regulate hair cell development. This knowledge can be used to build a regeneration therapy to re-grow new sensory cells. One possible avenue is to trigger conversion of non-sensory supporting cells to hair cells, an event that occurs naturally in non-mammalian species. We have recently shown the role of the transcription factor Prox1 during the development of the inner ear sensory epithelia (Kirjavainen et al., 2008). In this paper, we showed novel interactions between Prox1 and other transcription factors, which are likely to have significance in other developing tissues and in diseases as well. Our goal is to understand the regulation of Prox1 in the inner ear.

During recent years, we have focused on the cell cycle regulation in the inner ear, especially on the mechanisms that underlie the maintenance of postmitotic state of hair cells and on the fate of hair cells forced into the cell cycle. We have identified critical cell cycle regulators in this organ and shown that the postmitotic state is critical for the lifelong survival of hair cells (Mantela et al., 2005; Laine et al., 2007). We think that hair cells serve as excellent models to understand the restrictions in cell cycle progression in various types of differentiated cells, and the DNA damage response and DNA repair capacity of these cells. The goals of this research are to critically evaluate the potential of forced proliferation as a means to induce hair cell regeneration and, knowing the vulnerability of hair cells to chemotherapeutic drugs, to understand the molecular mechanisms behind the sensitivity of these cells to DNA lesion.