DiI-labeling reveals that normal innervation patterns (A, D) are disrupted by overexpression of BDNF (B, E) and loss of BDNF (C, F). By the first day of targeting (E14.5), wild type mice have very stereotyped innervation patterns, and each fiber bundle branch ends in a neural bud (A). Overexpression of BDNF throughout the epithelium increases branching and disrupts normal targeting (B, E). Very few neural buds are initially formed (B) and by E18.5 (E), few fungiform papillae are innervated. Innervation patterns are even more disrupted in Bdnf-/- mice. Axonal branching is extensive near the epithelial surface and neural buds fail to form (C). By E18.5, there is a loss of innervation throughout most of the tongue; however, a few neural buds were present, indicating that some fungiform papillae were innervated. Scale bar in A = 250 μm, applies to A-C; Scale bar in D = 500 μm, applies to D-F.