My broad research interests are in the area of sensory system development and regeneration. My research currently involves the mammalian inner ear. The mammalian organ of Corti is made up of hair cells and support cells that are arranged in a stereotyped pattern. My lab is interested in what signals are involved in the full differentiation of these various cell types and their potential for regeneration after hair cell loss. I am interested in what prevents the hair cells from regenerating after damage in mammals, as they do in birds and lower vertebrates. In particular I am exploring the role of FGFs in the development of the specific cell types in the mammalian cochlea. In the mouse the final steps in the development of the hearing organ occur postnatally and one of the last steps is the full development of the support cells, which surround the hair cells. I am particularly interested in a class of these support cells called Pillar cells. These cells are the rigid support cells that line the Tunnel of Corti and are known to be dependent on FGF signaling for their full differentiation.
We investigate all stages of the development of the mammalian cochlea using molecular and cellular techniques. A lab member may participate in explant culture experiments, identification of markers of differentiation for the various cells types by immunohistochemistry and in situ hybridization, examination of mutant animals using hearing testing and correlating this with changes in the cochlear histology and changes in specific markers of cell types. Looking at the expression patterns of certain molecules during development we hypothesize particular roles of these molecules during auditory development and then we test these hypotheses by both over expression and inhibition of the particular gene. In a similar way we are also looking at expression patterns in support cells after damage to the hair cells to see if they dedifferentiate and perhaps identify a window of opportunity during which it may be possible to coax these cells into regenerating the lost sensory cells of the cochlea.
With 10% of the population experiencing significant hearing loss figuring out how to regenerate the hair cells is an important goal. It is not clear if the most promising approach will be to use exogenous stem cells or to attempt to stimulate inherent cells to divide and differentiate. In lower vertebrates there is a re-expression of developmental genes after damage and this leads to regeneration. The mammalian cochlea fails to regenerate and this re-expression of the developmental program appears to be blocked. By analyzing developmental genes after loss of hair cells we hope to identify where the block in the pathway occurs. Once it is known where the pathway is blocked then it is possible to explore ways of re-initiating the developmental program to promote regeneration in the mammalian cochlea.
1: Hayashi T, Ray CA, Bermingham-McDonogh O. Fgf20 is required for sensory epithelial specification in the developing cochlea. J Neurosci. 2008 Jun 4;28(23):5991-9.
2: Hayashi T, Kokubo H, Hartman BH, Ray CA, Reh TA, Bermingham-McDonogh O. Hesr1 and Hesr2 may act as early effectors of Notch signaling in the developing cochlea. Dev Biol. 2008 Apr 1;316(1):87-99.
3: Hartman BH, Hayashi T, Nelson BR, Bermingham-McDonogh O, Reh TA. Dll3 is expressed in developing hair cells in the mammalian cochlea. Dev Dyn. 2007 Oct;236(10):2875-83.
4: Hayashi T, Cunningham D, Bermingham-McDonogh O. Loss of Fgfr3 leads to excess hair cell development in the mouse organ of Corti. Dev Dyn. 2007 Feb;236(2):525-33.
5: Bermingham-McDonogh O, Oesterle EC, Stone JS, Hume CR, Huynh HM, Hayashi T. Expression of Prox1 during mouse cochlear development. J Comp Neurol. 2006 May 10;496(2):172-86.