The long-term goal of this study is to understand the cellular and molecular processes involved in the early patterning of the developing inner ear, in particular the origin and differentiation of the sensory organs. In recent studies, specific genes have been used to identify regions fated to form sensory organs of the inner ear well before morphological differentiation. However, these genes have not been demonstrated to be true lineage markers for presumptive sensory regions of the inner ear. Proposed experiments will determine which regions of the otic placode give rise to sensory organs by studying the cell lineage directly. Furthermore, fate maps will be correlated with known gene expression patterns. The sensory organs consist of two cell types: hair cells, the highly specialized postmitotic mechanosensory cells, and supporting cells, which surround the hair cells. These two cells arise from a field of equipotent cells during sensory organ differentiation. Lateral inhibition through Notch/Delta signaling has been shown to be an important mechanism for generating different cell types from a domain of equipotent cells during neural development in Dros. Moreover, Notch and it's ligands, Delta and Serrate, are expressed in the frog inner ear at the time of hair cell differentiation. Hence, I propose to study the role of Notch/Delta signaling in the generation of hair cell and supporting cells of sensory organs. Advances in vital dyes, intra-vital imaging and gene function assays in the African clawed frog, Xenopus laevis, offer an unique opportunity to test proposed hypotheses in living embryos and tadpoles.
