Permanent loss of vestibulocochlear ganglion neurons and/or inner ear sensory epithelial cells is a major cause of deafness and vestibular dysfunction in humans. The identification and characterization of embryonic progenitors that give rise to these highly differentiated cell types is, therefore, an important step toward the goal of repairing the damaged auditory/vestibular pathway. Experiments described in this application will genetically mark a specific region of the source epithelium from which neurons and inner ear sensory cells are derived during embryogenesis. This will allow for: a) in vivo fate mapping of the marked region; and b) isolation of progenitor cells from the marked region by fluorescence activated cell sorting FACS) for in vitro analyses of developmental potential. In vitro studies will be aimed at optimizing conditions or generating differentiated neurons from isolated progenitors and testing the effects of various candidate signaling systems on neurogenesis. In addition, in vitro clonal analyses will test the hypothesis that neurons and sensory hair cells can be derived from a common, molecularly-defined progenitor cell. ? ?
| Raft, Steven; Koundakjian, Edmund J; Quinones, Herson et al. (2007) Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development. Development 134:4405-15 |
