A better sense of taste

Summary

The sense of taste informs our nutritive choices, which are essential for life and quality of life. Knowledge of taste bud development and maintenance will contribute to (1) understanding how taste sensitivity is determined, (2) developing proper therapeutic methods for patients with taste disorders, and (3) increasing food intake of animals in the meat and milk industry.

Situation

The sense of taste informs our nutritive choices, which are essential for life and quality of life. To identify and guide ingestion of appropriate nutrients, which regulates homeostasis and body mass, taste function must be intact. Lack of basic information about taste organ development is a main impediment for understanding emergence of taste disorders that deregulate ingestion. In mammals, taste bud cells in lingual taste papillae transduce chemical stimuli into signals conveyed to the central nervous system. The field of taste biology lacks a clear understanding of what constitutes possible taste cell precursors in developing papillae. There is no detailed, complete information about cell differentiation of the early lingual epithelium and how the underlying mesenchyme signals to lingual epithelium in papilla differentiation. Studies on fundamental issues, e.g., cell origin, differentiation and mesenchymal interactions of taste papilla and taste bud cells, will bring new information and perspective to the field of how the distribution and density of tongue taste organs are determined.

Response

To address the fundamental issues about origin and differentiation of taste papillae and taste buds, we have been using transgenic mouse lines and tongue organ culture system for morphological and functional analysis. An R01 grant has been funded by NIDCD NIH for this research program. The proposed studies are to address fundamental issues about formation of the taste papilla organ using modern techniques (Cre-mediated genetic modifications) and combination of in vivo and in vitro studies. Our goals are to: (Aim 1) demonstrate the optimal stage (1a) and primary cranial region (midbrain or hindbrain) (1b) of NC cell migration into the epithelium of tongue primordium; when and how many these cells differentiate in lingual epithelium to acquire specific cell phenotypes (1c); what types and proportions of taste bud cells are derived from NC (1d); (Aim 2) characterize how the BMP signaling in tongue mesenchymal NC derived cells, via distinct type I receptors (ALK2 and ALK3), interacts with the overlying epithelium in the development and maintenance of tongue, taste papillae and taste buds, with genetic modifications to (2a) down-regulate BMP signaling activity with Wnt1-Cre driven conditional knockout of Alk2 or Alk3; and (2b) up-regulate BMP signaling with Wnt1-Cre driven conditional constitutive activation of each receptor.

Impact

Our data on neural crest (NC) derived cell distributions in lingual epithelium, and on phenotypic alterations of tongue and taste papillae induced by genetic modifications in mesenchymal NC derived cells, suggest neural crest contributions to both epithelium and mesenchyme in the formation of taste organs. Cre-mediated, tissue-specific, genetic labeling and modifications provide powerful tools for these cell lineage assays and functional analyses. Two well-characterized transgenic mouse lines for NC assays, Wnt1-Cre and P0-Cre, are used. We have found that: (1) In tongue epithelium, both Wnt1-Cre and P0-Cre labeled NC derived cells are seen including taste papillae and taste buds (abundant in P0-Cre, infrequent in Wnt1-Cre) suggesting a potential NC derivation of taste cells which leads to a new concept in the field. P0-Cre labeled cells are first distributed in single, scattered elements at early stages to a clustered pattern later in taste papillae and taste buds. We propose that the single, scattered P0-Cre labeled epithelial cells are NC precursors and these will undergo cell differentiation to specific cell types in taste papillae and taste buds. (2) In tongue mesenchyme, Wnt1-Cre labeled NC derived cells are closely associated with taste papillae and taste buds. Wnt1-Cre driven, conditional genetic modifications of type I receptors Alk2 and Alk3 for bone morphogenetic proteins (BMPs) significantly alter the tongue, taste papilla and taste bud formation and maintenance in a level-, stage- and receptor-specific manner. This suggests that BMP signaling in tongue mesenchyme, via distinct receptors, interacts with the overlying epithelium for different roles in the development of tongue, taste papillae and taste buds. Overall, our studies for demonstration of cell origin, differentiation and mesenchymal interactions in taste papillae and taste buds contribute to understanding development of the taste organ and will bring new information and novel perspectives to the field for what constitutes taste cell precursors.

State Issue

S.E.T. - Science, Engineering, and Technology

Details

• Year: 2016
• Geographic Scope: International
• County: Clarke
• Program Areas:
  • Agriculture & Natural Resources