The field of taste has identified several regulatory molecules that direct development of the fungiform papilla: the sense organ residence of taste buds on the anterior tongue. However, the complexity of the papilla taste organ, composed of specific signaling compartments and encompassing both epithelial and connective tissues, has been ignored. Furthermore, specific differences in gene expression in fungiform papilla-forming versus papilla-free tongue regions have not been explored. This application focuses on the concept that only with knowledge about gene expression and protein localization in particular regions of the tongue and compartments of the fungiform papilla can a clear understanding emerge about how papilla development is regulated. Tongue regions and papilla compartments are physiological units that integrate signals to balance cell responses of proliferation or differentiation. Thus, cell signaling proceeds in the confines of particular compartments that then signal back and forth to define papilla induction, development and differentiation. The working hypothesis is that the important morphogen, Sonic hedgehog controls fungiform papilla development, in a concentration dependent manner, through: (a) signaling to regulate cell proliferation in specific compartments and tongue regions;and, (b) interactions with signaling other molecular families. Approaches to test the hypothesis include use of reporter and transgenic mice;tongue organ cultures;gene arrays;and gene knockdown with siRNAs via transfection and electroporation. Three specifc aims are to: Probe stage and compartment specific roles for the important morphogen, Sonic hedgehog (Shh), in cell proliferation versus differentiation. Define, and explore roles for, compartment specific genes in the developing tongue and tongue cultures, comparing lingual tissues in conditions that are papilla-replete, papilla-superabundant, papilla-suppressed, or papilla-free. Determine interactions among Shh, Wingless (Wnt) and Bone morphogenetic protein (Bmp) families. Studies will add crucial depth to understanding fungiform papilla formation;depth that is essential to knowing how papilla- and taste cell- specific compartments arise. In turn knowledge about signaling compartments in papilla differentiation is fundamental to pursuing questions about the origins of specific taste cell constitution, control of papilla and taste cell renewal, and papilla and taste cell plasticity during development. This knowledge is essential for acquiring basic information about how taste sensation emerges, to ultimately direct our diet and food choices.

Public Health Relevance

The sense of taste is life-essential, in directing identification and ingestion or rejection of nutrients. Taste buds reside, in the tongue, in taste papillae which are complex sensory organs. Thus developing papillae contain cell and molecular information that ultimately determines taste bud formation. To understand the developmental origins of nutrient selection, and the extent to which genetic makeup or early food experience can determine food preferences and aversions, basic knowledge is needed about how the taste papilla sense organs develop. It is necessary to know what periods of papilla development are rigidly determined and what periods are vulnerable to influence from substances that cross the placenta after maternal ingestion or access. Understanding the basic developmental biology of taste papillae also will provide insight into formation of taste bud-sensory nerve interactions that set up the neural circuits for taste sensation.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000456-25
Application #
8495304
Study Section
Special Emphasis Panel (ZRG1-IFCN-E (02))
Program Officer
Sullivan, Susan L
Project Start
1988-02-01
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
25
Fiscal Year
2013
Total Cost
$297,841
Indirect Cost
$104,381
Name
University of Michigan Ann Arbor
Department
Biology
Type
Schools of Dentistry
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Liu, Hong Xiang; Ermilov, Alexandre; Grachtchouk, Marina et al. (2013) Multiple Shh signaling centers participate in fungiform papilla and taste bud formation and maintenance. Dev Biol 382:82-97
Liu, Hong-Xiang; Grosse, Ann S; Iwatsuki, Ken et al. (2012) Separate and distinctive roles for Wnt5a in tongue, lingual tissue and taste papilla development. Dev Biol 361:39-56
Liu, Hong-Xiang; Henson, Bradley S; Zhou, Yanqiu et al. (2008) Fungiform papilla pattern: EGF regulates inter-papilla lingual epithelium and decreases papilla number by means of PI3K/Akt, MEK/ERK, and p38 MAPK signaling. Dev Dyn 237:2378-93