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Immunohistochemical distribution of growth-associated protein 43 (GAP-43) in developing rat nasoincisor papilla.

We employed immunohistochemistry of growth-associated protein 43 (GAP-43) to trace the early development of gustatory nerves and alpha-gustducin to demonstrate mature taste buds in the rat nasoincisor papilla (NP). The sequential changes of gustatory structures revealed eight characteristic stages. One, at embryonic day 16 (E16), GAP-43-immunoreactive (IR) nerve fibers were observed in close relation with presumptive taste buds in the lateral apical epithelium on each side of NP; meanwhile, no immunoreactivity could be observed in the papillary epithelium. Two, at E17, fine GAP-43-IR nerve fibers first invaded the apical epithelium of the papilla. Three, at E19, GAP-43-IR nerve fibers were extensive in apical epithelium and colonized in immature taste buds. Four, at E20, GAP-43-IR nerve fibers were first observed in ductal epithelium (lining the medial wall of nasoincisor ducts). Five, at postnatal day 1 (P1), immunoreactive nerve fibers first coincided with immature taste buds in the ductal epithelium. Six, at P3, alpha-gustducin-IR cells identical for mature taste buds were simultaneously demonstrated in both apical and ductal epithelium. Seven, at P14, progressive taste bud proliferation and maturation as well as neural invasion were demonstrated in all regions of the epithelium. Eight, during advanced stage in adult animals, extensive innervation was traced especially in close relation with taste buds. The sequential topographic patterns of NP gustatory structures seem very specific as compared to those in other locations of mammalian gustatory system. The present study reveals that gustatory nerves preceded the development of taste buds. However, further investigations are required to examine such a characteristic model for the neurogenic theory of taste induction.