The University of Michigan School of Dentistry
Dr. Mistretta's research is to understand early development and differentiation of the taste system. Current projects in the laboratory include study of developmental interactions between embryonic neurons in geniculate, petrosal and trigeminal ganglia and their sensory target organs in the tongue - the taste papillae and resident taste buds. In addition, experiments address the role of neurotrophins in promoting neurite outgrowth and regulating differentiation of neurophysiological properties of embryonic ganglion cells. The nature of the molecular exchange between tongue epithelium and mesenchymal tissues during formation of taste papillae, in advance of neurite growth into the tongue, is also being investigated.
The Mistretta lab studies development, maintenance, renewal and regeneration of the taste system. Our current focus is on the role of Hedgehog (HH) signaling in maintaining and renewing the progenitor cells for the complex lingual sensory organs of taste papilla and taste buds. The tongue is a biologically interesting readout for morphogen signaling, not only on merits as a collection of taste organs but also because it has shared tissue, cell and molecular features of both skin and intestine. The tongue is covered with a stratified squamous epithelium that includes non-taste and taste papillae (links to skin) and taste bud cells of “simple” epithelial biology that reside within the taste papillae (links to intestine). Both taste papilla cells and resident taste bud cells turn over in a continuous replacement cycle that renders the taste organ elements especially plastic or susceptible to metabolic and environmental events. Yet despite constant taste bud and epithelial cell renewal and replacement, and dynamic connective tissues, the taste organs maintain structural and functional sensory integrity. Therefore, for functional homeostasis, taste papilla organs including the taste buds require regulation of survival, proliferation, differentiation, and renewal of epithelial cells, with a maintained stroma and nerves.
In collaborative experiments with colleagues in the Medical School, data from transgenic mouse models demonstrate that postnatal HH signaling is an essential regulator of adult tongue epithelium, taste papillae and taste buds, with relatively short activation periods. Further we are studying the importance of understanding the Hedgehog pathway in tongue and taste organ renewal and maintenance when pathway-altering drugs are administered in human patients, with potential for disturbing taste function.
Our methods are cell biological and neurophysiological, using peripheral nerve recordings to measure functional taste responses with HH pathway alteration. Sensory homeostasis demands balanced cell physiology, and physiological adjustments in major signaling pathways can alter taste function and create risk for diet selection, toxin avoidance and proper nutrition. We find that HH signaling is essential to preserve homeostasis in taste organs; therefore balance in this pathway is crucial for taste sensation and nutrient regulation. Other current projects are (1) to understand interactions between innervation and HH signaling in taste organ maintenance and regeneration; (2) to identify location and types of mechanoreceptors in the tongue; (3) to determine whether Atoh1-positive cells in the tongue are in a lineage that contributes to taste organs; (4) to study neural crest derived cell contributions to tongue and taste organs.