Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.


Anatomical Sciences and Neurobiology

Committee Chair

Krimm, Robin Frances

Author's Keywords

Taste; Development; Neurotrophins receptors


Taste; Taste buds


Brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) are two neurotrophins that play distinct roles in geniculate (taste) neuron survival, taste innervation and taste bud formation. These two neurotrophins activate the same receptors tyrosine kinase B (TrkB) and a pan-neurotrophin receptor (p75). While the roles of these neurotrophins have been well studied, it remains unclear how much BDNF and NT-4 function through TrkB and p75 to regulate taste development in vivo. In chapter 2, I compared taste development in TrkB-/- mice and Bdnf-/-/Ntf4-/- mice to determine if these deficits were similar. If so, this would indicate that the functions of both BDNF and NT-4 can be accounted for by TrkB signaling. I found that TrkB-/- mice and Bdnf-/-/Ntf4-/- mice lose the same number of geniculate neurons by E13.5, indicating that BDNF and NT-4 primarily function through TrkB to regulate geniculate neuron survival. Surprisingly, the few geniculate neurons remaining in TrkB-/- mice are more successful in innervating the tongue and taste buds than those remaining in Bdnf-/-/Ntf4-/- mice. As a result these remaining neurons in the TrkB-/- mice innervate and support the development of a surprising number of taste buds. In addition, these remaining neurons do not express the TrkB receptor, indicating the either BDNF or NT-4 must function through an additional receptor to influence taste innervation and/or targeting. The p75 receptor can function as either a pro-survival or pro-death factor during peripheral nervous system development. However, the role of p75 in taste development is unknown. In chapter 3, I examined neuron survival, taste bud formation and tasteinnervation in the p75-/- and TrkB-/-/p75-/- mice. I found that at E13.5, the age after BDNF and NT-4 dependence is established, p75-/- mice did not lose geniculate neurons compared to the wild type mice. This finding indicates that p75 does not mediate neurotrophin neuronal survival at or before this age. Hybrid TrkB-/-/p75-/- mice had the same number of geniculate neurons as TrkB-/- mice, suggesting that p75 does not induce neuron death in the absence of Trk-signaling like it does for some other systems. By E14.5, there is a loss of geniculate neurons in p75-/- mice which continues until E18.5. Also at this age, the pattern of chorda tympani nerve innervation was disrupted in the p75-/- mice. Specifically, the nerves avoid innervating the mid-region of the tongue. Due to the loss of innervation, the taste bud number was decreased in the p75-/- mice. It is possible that the neuron loss is due to this disrupted innervation pattern. Interestingly, TrkB-/-/p75-/- mice have more taste buds than p75-/- mice. These additional taste buds are not innervated which suggests that p75 may function as a pro-death factor in the taste bud during development. Taken together, my results suggest that p75 does not mediate the neurotrophin survival function for taste neuron development. Instead, it is important for taste innervation and branching to the tongue middle line and could influence taste cell survival in the absence of innervation and/or neurotrophin signaling.