Neurothrophins in the development of the gustatory system and teeth

Flavors of taste are detected by a set of microscopical cellular aggregates called the taste buds, present in different arrangements on the upper surface of the tongue and other areas in the mouth. Taste buds are chemosensors that can detect different taste qualities such as sweet, sour, bitter, salt and umami. Information from the taste buds is carried via nerve fibers to the brain where these signals are further processed, finally leading to the experience of taste. Taste buds not only help us enjoy food, they are also part of an important control and warning system, enabling us to avoid consuming hazardous substances or spoiled food. During the past several years, more light has been shed on many aspects of the gustatory system, including the local epithelial origin of taste buds and taste transduction mechanisms. However, the manner in which taste buds develop and become connected to the brain by nerve fibers has long been a matter of debate. The present work now demonstrates the crucial importance of two proteins closely related to nerve growth factor (NGF) in tastebud development and proper taste and sensory functions of the mouth. Messenger RNA coding for the NGF-related proteins BDNF (brain derived neuro trophic factor) and NT-3 (neurotrophin-3) were found to be present in precisely the right locations in and around the taste buds to suggest that they are of vital importance for controlling the arrival of nerve fibers to these structures. These hypotheses were borne out by studies of mice in which either the gene for BDNF or NT-3 had been selectively turned off. Mice that developed without BDNF had very few and abnormal taste buds and were unable to discriminate between primary tastes such as sweet, salt or bitter. Animals in which the NT-3 gene had instead been turned off appeared to have a normal development of their taste bud system, but instead demonstrated severe impairment of sensory function of mucous membranes of the oral cavity. These results demonstrate key roles for the two neurotrophic proteins BDNF and NT-3 in con trolling the development of the gustatory and somatosensory apparatuses of the mouth. These neurotrophins also seem to be important in oral gustatory and somatosensory innervation in humans. It remains to be seen whether or not disturbances of the genes for these neurotrophic proteins might underlie rare human conditions such as familial dysautonomia in which the ability to discriminate tastes is lost. These novel findings may also have implications in more common cases in problems of loss of taste and sensation in the mouth such as those seen after injury to the nerves, either by accident or following oral or facial surgery. Knowledge about which proteins are needed to stimulate nerve fibers to grow into mucous membranes of the oral cavity during development suggests that these same proteins might become helpful in stimulating regeneration of injured nerves in adult patients, perhaps helping them to regain lost taste and sensory function. Neurotrophins are also expressed in the developing teeth. They all show temporospatially specific expression patterns. We suggest that neurotrophins are involved in early morphogenetic events during tooth development and that NGF and BDNF are involved in the innervation of the dental pulp. Further experiments are required to determine the precise roles of neurotrophins in tooth development. The GDNF family of ligands and receptors are also expressed in developing tongue and teeth. They might be involved in the autonomic innervation of the tongue. In teeth, they might participate both in morphogenetic events during tooth development and participate in tooth innervation