Review
Developing a sense of taste

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Abstract

Taste buds are found in a distributed array on the tongue surface, and are innervated by cranial nerves that convey taste information to the brain. For nearly a century, taste buds were thought to be induced by nerves late in embryonic development. However, this view has shifted dramatically. A host of studies now indicate that taste bud development is initiated and proceeds via processes that are nerve-independent, occur long before birth, and governed by cellular and molecular mechanisms intrinsic to the developing tongue. Here we review the state of our understanding of the molecular and cellular regulation of taste bud development, incorporating important new data obtained through the use of two powerful genetic systems, mouse and zebrafish.

Highlights

► Early induction and patterning of taste buds occur via processes inherent to the developing tongue. ► Interactions of the Wnt, BMP, Shh and FGF pathways regulate early taste bud formation. ► Signals from the mesenchyme to the overlying epithelium are important regulators of taste bud pattern. ► FGF, Notch and miR-200 signaling control cell fate decisions within multicellular taste buds. ► Molecular genetic approaches in both mouse and zebrafish underlie recent advances in our understanding of taste development.

Introduction

Taste is a primary sense of all vertebrates, reliably conveying important chemical information from the mouth to the brain to regulate ingestion. For most animals, sweet, moderately salty or certain amino acid stimuli trigger appetitive behavior, while bitter or sour substances typically are rejected. The ability of animals to distinguish between nutritional, versus potentially lethal, fermented or unripe food items may mean the difference between survival and death. Human beings also rely on the taste system to select delicious foods and beverages based, in part, on taste preferences for the 5 basic taste stimuli; sweet, sour, salt, bitter, and umami (the taste of glutamate). Because taste is involved in ingestive behavior, this sensory system is inherently linked to human diseases that result from obesity, such as stroke, heart disease and diabetes.

Taste buds are multicellular receptor organs that transduce taste stimuli in the oral cavity. Multiple taste cells within buds are innervated by cranial nerve fibers, which in turn convey taste information to the brain. For nearly a century, taste buds were thought to be induced by nerve contact late in embryonic development. Over the past decade, however, this view has shifted dramatically. A host of studies now indicate that taste bud development is initiated and proceeds via processes that are nerve-independent, occur long before birth, and are governed by cellular and molecular mechanisms intrinsic to the developing tongue. Thus our primary focus here is a review of recent advances in our understanding of the molecular and cellular mechanisms of taste bud development that occur in the embryonic oropharynx.

Another aspect of our review is to emphasize the progress made in detailed mapping of the fates of embryonic cell populations that contribute to the developing taste periphery. In large part, these studies have entailed use of cutting edge molecular genetic mouse models, and each has provided new insights into the cellular mechanisms governing specification and differentiation of taste epithelium. These types of genetic tools have also been instrumental in revealing fundamental molecular machinery involved in these early processes.

Finally, while the focus of the field has for decades been on rodent model systems, more recently amphibian embryos, and now the genetic zebrafish and medaka systems are providing new insights and accelerating the pace of discovery. Here we highlight the newest molecular genetic data concerning taste bud development in fish.

Section snippets

The anatomy of the taste system of vertebrates

The sense of taste or gustation is mediated by multicellular taste buds, which reside primarily within the oral and pharyngeal cavities. Taste receptor cells transduce taste stimuli, i.e. sweet, bitter, sour, salt and umami, into electrochemical signals and transmit these signals to afferent nerve fibers of the VIIth, IXth and Xth cranial nerve ganglia, which in turn convey taste information to the first central taste relay located in the hindbrain, the nucleus of the solitary tract. To date,

Taste bud cellular composition in mice and fish

Each taste bud is composed of a heterogeneous population of fusiform cells, which parse into 3 morphological types (I, II and III), but physiologically likely represent at least 5 distinct functional classes (sweet, sour, salt, bitter and umami). Enormous advances have been made in our understanding of taste receptor cell function in the past decade, and these are reviewed elsewhere in this review volume (I. Matsumoto et al and references there in). Here we focus briefly on the conserved

Defining the embryonic origin of vertebrate taste buds

Taste buds are found in the epithelia lining the oral and pharyngeal cavity, and like epidermis of the skin, taste cells are continually renewed throughout adult life [37], [38]. Based on their location and this regenerative feature, taste bud cells have long been considered to be modified epithelial cells which therefore were presumed to arise directly from the local epithelium [39], [40]. Subsequently, this hypothesis was addressed experimentally; in axolotl (a type of salamander) [41]

Nerve-dependent induction

The prevailing model of taste bud development has been neural induction, where late in embryogenesis taste nerves invade the lingual epithelium and induce taste bud precursors from an otherwise homogeneously competent epithelium [47], [61], [62]. However, over the past 20 years, experimental tests have firmly rejected this hypothesis. Using both grafting and culture approaches combined with molecular marker expression, we showed that amphibian taste buds differentiate without innervation,

Molecular mechanisms of taste bud development

The focus of studies of taste bud development has now shifted from a neural induction model to processes intrinsic to the tongue, and in particular to investigations of the molecular mechanisms involved. To date, regulation of taste bud development involves a number of pathways known to play critical roles in a variety of tissues throughout development, as well as in adult homeostasis and disease. Foremost among these are the Shh and Wnt/β-catenin pathways. Here we review new data on the role

Conclusion

The sense of taste plays a key role in our ability to select palatable and nutritious foods, as well as to reject those substances that are toxic or decomposing. While our understanding of taste system function has expanded dramatically over the past 2 decades, how this system develops embryonically is only now receiving increased attention and study. Molecular genetic tools in mouse have become steadily more numerous and sophisticated, as well as more tractable for use in the taste system;

Acknowledgements

We are grateful to Frederic Rosa and IBENS (MK), and to the Rocky Mountain Taste and Smell Center (P30 DC004657) for support (LAB). This work was funded by the ANR-09-BLAN-077 (MK) and NIH/NIDCD DC008373 and DC003947 (LAB).

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