Characterizing the essential role of sonic hedgehog in taste bud development

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DESCRIPTION (provided by applicant): Taste buds are unique among sense organs in that they have neuronal properties yet arise from the local lingual epithelium and hence can be considered as modified epithelial appendages. Early stages of taste bud formation share some similarities with those of other epithelial appendages with the formation of a localized epithelial thickening called placode that undergo invagination with the underlying mesenchyme to form a papillae. Taste buds appear at the apices of papillary epithelium around birth. Similar interacting signaling pathways involved in formation of epithelial appendages also play a role in taste organ morphogenesis. Of these signaling molecules, Sonic hedgehog (SHH) has been implicated to play a significant role in taste organ morphogenesis. We recently demonstrated that SHH descendent early progenitor population of cells gives rise to majority of the functional adult taste cell types and this embryonic population being lost postnatally. This implicates that SHH descendent taste bud progenitors are signaling centers, which direct taste progenitor development early and papilla development later. In this proposal, I aim to test the early and late function of SHH in taste progenitor and papillary development respectively. I propose these studies by making use of powerful mouse molecular genetics tools with inducible cre lox technology in combination with dynamic time lapse live imaging of taste organ formation. Characterizing the nature of SHH function in terms of early and late development of taste organs is an important step in understanding molecular mechanisms involved in the process of taste organ formation.