Link to Homepage
Introduction
The tongue is an organ crucial to food mastication, the gustatory sense, and speech in human beings. The cells which perform these diverse functions have proven to have diverse embryonic origins as well. The information about tongue development presented here has been gathered from experiments with sheep, rats, and axolotl salamanders, as well as from studies in human anatomy. The development of the tongue itself, taste bud development, cell renewal within mature taste buds, and congenital defects of the tongue are all topics which will be discussed.
Notes on Tongue and Taste Bud Anatomy
The anterior two-thirds of the tongue, known as the oral part, and the posterior pharyngeal part of the tongue are separated by the terminal sulcus, a V-shaped depression (Figure 1). The dorsal surface of the most anterior part is covered with 25 to 75 fungiform papillae, which each contain one to six taste buds. Foliate papillae can be found on the sides of the posterior one-third of the tongue, while seven to ten circumvallate papillae lie along the groove of the terminal sulcus. Both of these latter types of papillae contain taste buds also. The filiform papillae that populate the entire dorsal surface of the tongue, however, are not equipped with taste buds. Taste buds are clusters of 80 to 100 neuroepithelial cells specialized for taste reception. Taste cells within the taste bud make synapses with afferent sensory nerves derived from the cranial nerves (Spielman et al. 1991, p528). The muscular root of the tongue is attached to the hyoid and mandible, while the posterior ventral part is connected to the oral floor by the frenulum (Williams et al. 1989, p1319).
Figure 1. Illustration of the dorsal side of the human tongue. (Williams et.al. 1989)
The Pharyngeal Arches
The pharyngeal arches, also termed branchial arches, are embryonic structures which play a large role in the development of the head and neck regions. In humans, they first appear early during the fourth week of gestation as four rounded ridges on either side of the developing head and neck (Figure 2). They are positioned just below the stomodeum, or primitive mouth depression, which is covered by the oropharyngeal membrane. This membrane ruptures at about the 24th day, bringing the oral cavity into contact with the embryoÕs external environment. The migration of neural crest cells into the mesenchyme of the pharyngeal arches causes them to enlarge. Each arch contains a rod of cartilage which supports the structure, a muscular component, and a nerve which is derived from the neuroectoderm of the primitive brain (Moore et al. 1993, p152-4). In between each arch lies a pair of pharyngeal pouches, which eventually give rise to the thymus, tonsils, and structures of the ear (Gilbert 1994, p361).
Figure 2. Scanning electron micrograph of a human embryo of approximately 33 days. From this ventral view, the four branchial arches are visible. (Moore et al. 1993)
Embryonic Tongue Development
A triangular elevation in the floor of the pharynx during the end of the fourth week of gestation is the first sign of the developing tongue. This elevation is called the median tongue bud. The proliferation of mesenchymal cells in the ventromedial areas of the first pharyngeal arches causes the formation of two oval buds on either distal side of the tongue. The oral part of the tongue forms when these distal tongue buds rapidly enlarge and fuse to overgrow the median tongue bud. Sensory innervation of this part is done by the lingual branch of the mandibular division of the trigeminal nerve, which originates in the first pharyngeal arch (Moore 1982, p195-6).
Behind the foramen cecum, two elevations called the copula and hypobranchial eminence (also referred to as the tuberculum impar) form to create the pharyngeal part of the tongue. The copula is eventually overgrown by the hypobranchial eminence. The median and pharyngeal sections of the organ then become joined at the terminal sulcus. This posterior section of the tongue is innervated by the glossopharyngeal nerve, derived from the third pharyngeal arch (Moore 1982, p196-7). The growing tongue extends out into the oral cavity, covered by a layer of ectodermal epithelium. The root of the tongue, however, is covered with endodermal epithelium. These two tissues merge eventually so that their boundaries are undetectable (Feduccia et al., p285).
However, it is only the epithelial and mucosal tissues of the tongue which develop from the four pharyngeal swellings described above. The musculature of the tongue can be traced to another source. The majority of this muscle tissue descends from myoblasts which differentiate after migrating from the myotomes of the occipital cervical somites. Accompanying these myoblasts on their journey to the presumptive tongue region is the hypoglossal nerve, which generates the nerve supply for the tongue musculature. The mesenchyme of the pharyngeal arches forms connective tissue in the tongue region, lymphatic and blood vessels of the tongue, and probably some muscle tissue as well (Moore 1982, p196).
The musculature of the tongue is an important participant in the process of chewing and swallowing in vertebrates. The tongue manipulates food in the mouth for mastication; this mass of chewed food, called the bolus, is then pushed to the back of the oral cavity by the tongue. When contact is made with the soft tissue in the back of the mouth, the complex neurological reflex of swallowing is initiated (Purves et al. 1995, p995). As a result, the food is moved into the pharynx and then into the esophagus to await digestion.
Taste Bud Development
Farbman published an electron microscope study of embryonic rat fungiform papillae in 1965 which significantly increased our understanding of the processes and structures involved in taste bud development. The fungiform papillae first appear as ÒeminencesÓ on the dorsal side of the tongue that are composed of three layers of epithelial cells and also connective tissue closely associated with the basement membrane. Mitotically active regions appear in each epithelial layer. Nerves are not present at this stage, but they soon appear between seventeen and nineteen days of gestation. The nerve cells enter the region in one or two bundles, unmyelinated and surrounded by a Schwann cell. Next, groups of membrane-bound vesicles appear in the epithelium and the nerve terminal processes enter these vesicles and epithelial cells. The size of the papilla increases at this stage, and the epithelial cells grow in number; the connective tissue also becomes inhabited by blood vessels (Farbman 1965, p114-9).
Several changes take place in the developing rat fungiform papilla during the first week after birth. Surface cells become keratinized and other cells differentiate. Finally, as early as the twelfth postnatal day, a taste pore develops and the taste bud resembles a small form of the adult taste bud (p120). The taste pore is a break in the keratinized surface of the epithelium through which signals from the oral cavity can be received by the underlying sensory neurons (Figure 3). Microvilli often protrude from this opening (p131).
Figure 3. Scanning electron micrograph of a mud puppy taste pore. (Miller 1990)
Papillae in the human embryo appear at approximately day 54 of gestation. The fungiform papillae are innervated by the chorda timpani branch of the facial nerve of the second pharyngeal arch, while the vallate and foliate papillae are innervated by the glossopharyngeal nerve. It is known that reflex pathways are established between the taste buds and the facial muscles by the 28th week, since bitter responses are observed in the fetus by this point in gestation (Moore 1982, p196).
Researchers considered several tissues when determining the origin of taste buds in the vertebrate. These included the epibranchial placodes, which are epidermal thickenings in the cranial region (Gilbert 1994, p268); the neural crest cells; and the local epithelium of the oropharyngeal cavity. Epibranchial placodes are located just dorsal to the pharyngeal pouches and give rise to the facial, vagal, and cranial nerves which innervate the taste buds. Neural crest cells were considered as a candidate because they are key to the development of other vertebrate sensory systems and they give rise to other oral tissues like the odontoblasts (Barlow et al., p274). The epithelium of the tongue, where taste bud development is observed, was an obvious third choice.
In their 1994 experiment, Barlow et al. grafted tissue from each of these areas in pigmented axolotl embryos onto the appropriate regions in albino embryos (Figure 4). Axolotl salamanders were used because they recover extremely well after surgical procedures and because amphibian tissue survives well in culture (p1104). The researchers allowed the larvae to develop for an additional three days, until the mouth was fully formed and mature taste buds were visible. They then examined the taste buds for pigment granules, which reveal cell fate. Pigment was not present in the taste buds of embryos with epibranchial placode or neural crest grafts.
When they obtained this result, they hypothesized that the taste buds originated from the local oropharyngeal epithelium instead. This hypothesis was tested by labeling a region above the dorsal blastopore lip, known to give rise to the presumptive cephalic endoderm, with carbocyanine dye shortly after gastrulation had begun. Barlow et al. reports: ÒThe oropharyngeal epithelium of all animals infected as gastrulae and examined as swimming larvae contained polyclones of labeled cells which included both taste buds and generalized epithelial cellsÓ (p279). Thus, they could conclude that taste buds in the axolotl arise exclusively from local epithelial tissue.
Barlow et al. state that this is the first time that excitable vertebrate receptor cells which have been found to arise from nonectodermal tissue. Photoreceptors, olfactory neurons, lateral line mechano- and electroreceptors, and hair cells of the inner ear are all receptor cells which share a neuroectodermal origin. Secondly, they point out that the gustatory system is the first sensory system discovered to have dual origins; that is, it contains tissues derived from both endoderm (the taste buds) and ectoderm (sensory neurons) (p279). However, there are vertebrate species in which taste buds have been shown to arise from ectoderm. Several species of teleost fishes, for instance, have taste buds on the surface of the head and trunk which develop directly from the local ectoderm. The Barlow team did not conclude whether mammalian taste buds are derived from either ectoderm or endoderm, since the blending of both types of epithelium on the surface of the tongue makes mammalian taste bud development more difficult to chart (p283).
Many scientists have asserted that taste bud development is caused by interaction with nerve tissue and that functional taste buds do not form in the absence of innervation. This was thought to be a classic example of cell differentiation induced by a neighboring tissue (Farbman 1965, p110). However, this assumption was been challenged in a 1996 paper published by Barlow, Chien, and Northcutt. Several years of experimentation with axolotl embryos has suggested that this apparent neural induction is only a Òcoincidence of timingÓ (Barlow et al. 1996, p1103).
Prior to innervation by the cranial nerves, the presumptive oropharyngeal region was removed from pigmented axolotl embryos. Ectoderm was then removed from the trunks of albino embryos and replaced with the oropharyngeal grafts. Mature taste buds were indeed found in the trunk grafts in complete absence of innervation. In a second experiment, presumptive oropharyngeal areas were removed from axolotl embryos and placed in culture. Within six to ten days (by which time unmanipulated control embryos had reached stage 41 to 43), taste buds were again visible in the endoderm of the grafts. Thus, Barlow et al. concluded that taste bud development does not depend upon induction by the cranial nerves as was previously thought. Though the nerve tissue may not directly induce the differentiation of taste buds, there seems to be some sort of interaction going on between the two. There is evidence that the taste bud primordia actually attract nerve fibers to grow directly into them. In addition, fungiform papillae express a brain-derived neurotrophic factor (BDNF) mRNA when nerves enter the taste bud epithelium, and it has been suggested that Òthe restricted availability of this trophic factor may play a role in maintaining and stabilizing early neuritic contacts of gustatory sensory neurites with taste bud primordiaÓ (p1109).
It has been suggested that taste bud development is caused by either the patterning of morphogenic factors intrinsic to the oropharyngeal epithelium or by contact with an inducing tissue like the cephalic neural crest or paraxial mesoderm. Early distribution of the papillae primordia in the tongue epithelium corresponds to cartilaginous, neural crest-derived components of the oropharynx lying below it (p1109). Paraxial mesoderm is another candidate for the inducer because its contact with the oropharynx precedes the migration of the neural crest. Thirdly, there is evidence that Hox genes are involved in the determination of an endodermal anterior-posterior axis during gastrulation; Barlow et al. suggest that the specification of anterior tongue endoderm via this mechanism Òcould represent the first step in commitment of oropharyngeal epithelial cells toward a taste cell fateÓ (p1110).
Bradley and Mistretta have carried out experiments to investigate the timing of taste bud development in mammals (1972, 1978). They observed tongue development in fetal sheep and also tested the functionality of taste buds by first stimulating the tongue with various substances and then recording responses in the chorda tympani nerve (the sensory nerve of the taste bud). Bradley et al. found the first sign of taste pores at approximately 100 days of gestation. At this point, only one taste bud per papillae was observed; two buds were visible in some between 100 days and term and newborn lambs fungiform papillae could contain three or four taste buds (Bradley et al. 1972, p273).
Figure 4. Responses of taste neurons to six chemicals in a 105 -day sheep fetus and a 122-day fetus. (Mistretta et al. 1978)
Cell Renewal in Functional Taste Buds
In the environment of the human mouth, taste cells sustain constant abuse from food, abrasion, hot and cold liquids, and cigarette smoke. Despite this fact, one is always left with functioning taste buds. By necessity, therefore, taste buds do not undergo development solely during the embryonic stage. The cells of the taste bud are constantly being renewed throughout the life of an organism. It is estimated that a new cell moves into the taste bud every ten hours, and the turnover time for the total cell population of mouse tongue epithelium has been determined to fall between 4 and 8.4 days (Beidler et al. 1965, p269-70).
Congenital Tongue Defects
The failure of the distal tongue buds to fuse completely at the posterior of the tongue can result in cleft tongue, or a groove down the middle of the tongue. Bifid tongue, another defect in which the distal tongue buds do not fuse, is seen most commonly in South American babies. Macroglossia, the presence of an abnormally large tongue, is caused by lymphangioma or muscular hypertrophy in the tongue. Microglossia, conversely, results in the development of an abnormally small tongue; it is usually caused by micrognathia, or an underdeveloped jaw with recession of the chin. One in 300 North American newborns have a condition called ankyloglossia, or tongue-tie, in which the frenulum extends almost the length of the tongue and thus inhibits tongue movement (Moore 1982, p197).
Summary
The development of the tongue and taste is still, for the most part, a mysterious subject. Cells of the tongue are derived during embryogenesis from the tissue of the pharyngeal arches, myoblasts of the somites, and quite possibly from other regions such as the neural crest. Most recently, research about the development of the tongue and taste has focused on questions about the origins of the taste buds cells and the process by which they are induced to differentiate.
Barlow, L.A, C.Chien, and R.G.Northcutt. Embryonic taste buds develop in the absence of innervation. Development, 122:1103-111, 1996.
Barlow, L.A. and R.G.Northcutt. Embryonic origin of amphibian taste buds. Developmental Biology, 169:273-85, 1995.
Beidler, L.M and R.L.Smallman. Renewal of Cells Within Taste Buds. J. Cell Biology, 27: 263 71, 1965.
Bradley, R.M. and C.M.Mistretta. The gustatory sense in foetal sheep during the last third of gestation. J. Physiology, 231:271-82, 1973.
Farbman, A I. Electron Microscope Study of the Developing Taste Bud in Rat Fungiform Papilla. Developmental Biology, 11:110-35, 1965.
Feduccia, A. and E.McCrady. TorreyÕs Morphogenesis of the Vertebrates, 5th ed. New York: John Wiley & Sons, Inc., 1991.
Gilbert, S.F. Developmental Biology, 4th ed. Sunderland, MA: Sinauer Associates, 1994.
Hill, D.L. and P.R.Prezekop, Jr. Influences of Dietary Sodium on Functional Taste Receptor Development: A Sensitive Period. Science, 241:1826-7, 1988.
McLaughlin, S. and R.F.Margolskee. The sense of taste: The internal moleular workings of the taste bud help it distinguish the bitter from the sweet. American Scientist, 82:538-45, 1994.
Miller, J.A. A matter of taste: Innovative methods and materials open new view of gustatory biology. BioScience, 40:78-82, 1990.
Mistretta, C.M. and R.M.Bradley. Taste responses in sheep medulla: changes during development. Science, 202:535-37, 1978.
Moore, K.L. The Developing Human: Clinically oriented human embryology, 3rd ed. Philadelphia: W.B. Saunders Co., 1982.
Moore, K.L. and T.V.N.Persaud. Before We Are Born: Essentials of Embryology and Birth Defects, 4th ed. Philadelphia: W.B. Saunders Co., 1993.
Purves, W.K., G.H.Orians, and H.C. Heller. Life: The Science of Biology, 4th ed. Sunderland, MA: Sinauer Associates, 1995.
Spielman, A.I., J.G.Brand, M.R.Kare. "Tongue and Taste" in The Encylcopedia of Human Biology. Sand Diego: Academic Press, 7:527-35, 1991.
Stewart, R.E. and D.L.Hill. Time course of saline-induced recovery of the gustatory system in sodium-restricted rats. Am. J. Physiology, R704-11, 1996.
Williams, P.L., R.Warwick, M.Dyson, L.H.Bannister. Gray's Anatomy. Edinburgh: Churchill Livingstone, 1989.