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.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-E (02))
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Sullivan, Susan L
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University of Michigan Ann Arbor
Schools of Dentistry
Ann Arbor
United States
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Kumari, A; Yokota, Y; Li, L et al. (2018) Species generalization and differences in Hedgehog pathway regulation of fungiform and circumvallate papilla taste function and somatosensation demonstrated with sonidegib. Sci Rep 8:16150
Boggs, Kristin; Venkatesan, Nandakumar; Mederacke, Ingmar et al. (2016) Contribution of Underlying Connective Tissue Cells to Taste Buds in Mouse Tongue and Soft Palate. PLoS One 11:e0146475
Kumari, Archana; Ermilov, Alexandre N; Allen, Benjamin L et al. (2015) Hedgehog pathway blockade with the cancer drug LDE225 disrupts taste organs and taste sensation. J Neurophysiol 113:1034-40
Scanlon, Christina Springstead; Banerjee, Rajat; Inglehart, Ronald C et al. (2015) Galanin modulates the neural niche to favour perineural invasion in head and neck cancer. Nat Commun 6:6885
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; Komatsu, Yoshihiro; Mishina, Yuji et al. (2012) Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds. Dev Biol 368:294-303
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
Wilson, Donald A; Baker, Harriet; Brunjes, Peter et al. (2009) Chemoreception scientists gather under the Florida sun: The 31st Annual Association for Chemoreception Sciences meeting. Ann N Y Acad Sci 1170 Suppl 1:1-11
Liu, Hong-Xiang; Grosse, Ann M Staubach; Walton, Katherine D et al. (2009) WNT5a in tongue and fungiform Papilla development. Ann N Y Acad Sci 1170:11-7
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