Epithelial overexpression of BDNF or NT4 disrupts targeting of taste neurons that innervate the anterior tongue

Brain-derived neurotrophic factor (BDNF) and neurotrophin-il (NT4) are esse ntial for the survival of geniculate ganglion neurons, which provide the se nsory afferents for taste buds of the anterior tongue and palate. To determ ine how these target-derived growth factors regulate gustatory development, the taste system was examined in transgenic mice that overexpress BDNF (BD NF-OE) or NT4 (NT4-OE) in basal epithelial cells of the tongue. Overexpress ion of BDNF or NT4 caused a 93 and 140% increase, respectively, in the numb er of geniculate ganglion neurons. Surprisingly, both transgenic lines had severe reduction in fungiform papillae and taste bud number, primarily in t he dorsal midregion and ventral tip of the tongue. No alterations were obse rved in taste buds of circumvallate or incisal papillae. Fungiform papillae were initially present on tongues of newborn BDNF-OE animals, but many wer e small, poorly innervated, and lost postnatally. To explain the loss of ne rve innervation to fungiform papillae, the facial nerve of developing anima ls was labeled with the lipophilic tracer DiI. In contrast to control mice, in which taste neurons innervated only fungiform papillae, taste neurons i n BDNF-OE and NT4-OE mice innervated few fungiform papillae. Instead, some fibers approached but did not penetrate the epithelium and aberrant innerva tion to filiform papillae was observed. In addition, some papillae that for med in transgenic mice had two taste buds (instead of one) and were frequen tly arranged in clusters of two or three papillae. These results indicate t hat target-derived BDNF and NT4 are not only survival factors for geniculat e ganglion neurons, but also have important roles in regulating the develop ment and spatial patterning of fungiform papilla and targeting of taste neu rons to these sensory structures. (C) 2001 Academic Press.