Receptor tyrosine kinases are known to play a key role in the development of non-neuronal cells in neural tissue. Recent data from investigations of FGF receptors in the developing cochlea have shown that a specific FGF receptor FGFR3 is required for the differentiation of a group of glial-like support cells of the inner ear's sensory epithelium, the pillar cells. This system provides the unique advantage of having a highly stereotyped population of glial-like cells that can be readily identified. The experiments outlined in this proposal will lead to further understanding of the molecular mechanisms that control the differentiation of this important type of support cell, with the following specific aims. 1. To determine the time in development when Fgfr3 is first required for Pillar cells. 2. To examine pillar cell development in mice with constitutively activated mutations. 3. To examine the expression of candidate FGFR3 ligands in the developing cochlea. 4. To examine the effect on Pillar cell differentiation of elimination of FGF8 from the inner hair cells at different stages of development. 5. To determine whether FGF8 can promote pillar cell differentiation. The studies we have proposed will extend our understanding of the role of FGF-FGFR signaling in the development and maintenance of the differentiated phenotypes in the cochlea; our long term aims are to use this information to better understand congenital defects in this system and to ultimately promote its repair.
| Bermingham-McDonogh, Olivia; Corwin, Jeffrey T; Hauswirth, William W et al. (2012) Regenerative medicine for the special senses: restoring the inputs. J Neurosci 32:14053-7 |
| Munnamalai, Vidhya; Hayashi, Toshinori; Bermingham-McDonogh, Olivia (2012) Notch prosensory effects in the Mammalian cochlea are partially mediated by Fgf20. J Neurosci 32:12876-84 |
| Bermingham-McDonogh, Olivia; Reh, Thomas A (2011) Regulated reprogramming in the regeneration of sensory receptor cells. Neuron 71:389-405 |
| Hayashi, Toshinori; Lamba, Deepak A; Slowik, Amber et al. (2010) A method for stabilizing RNA for transfection that allows control of expression duration. Dev Dyn 239:2034-40 |
| Hartman, Byron H; Nelson, Branden R; Reh, Thomas A et al. (2010) Delta/notch-like EGF-related receptor (DNER) is expressed in hair cells and neurons in the developing and adult mouse inner ear. J Assoc Res Otolaryngol 11:187-201 |
| Hartman, Byron H; Reh, Thomas A; Bermingham-McDonogh, Olivia (2010) Notch signaling specifies prosensory domains via lateral induction in the developing mammalian inner ear. Proc Natl Acad Sci U S A 107:15792-7 |
| Hayashi, Toshinori; Ray, Catherine A; Younkins, Christa et al. (2010) Expression patterns of FGF receptors in the developing mammalian cochlea. Dev Dyn 239:1019-26 |
| Hayashi, Toshinori; Kokubo, Hiroki; Hartman, Byron H et al. (2008) Hesr1 and Hesr2 may act as early effectors of Notch signaling in the developing cochlea. Dev Biol 316:87-99 |
| Hayashi, Toshinori; Ray, Catherine A; Bermingham-McDonogh, Olivia (2008) Fgf20 is required for sensory epithelial specification in the developing cochlea. J Neurosci 28:5991-9 |
| Hartman, Byron H; Hayashi, Toshinori; Nelson, Branden R et al. (2007) Dll3 is expressed in developing hair cells in the mammalian cochlea. Dev Dyn 236:2875-83 |
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