The neurotrophin receptor p75 regulates gustatory axon branching and promotes innervation of the tongue during development

Background: Brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) regulate the survival of gustatory neurons, axon growth and branching, and innervation of taste buds during development. These actions are largely, but not completely, mediated through the tyrosine kinase receptor, TrkB. Here, we investigated the role of p75, the other major receptor for BDNF and NT4, in the development of the taste system. Results: We found that p75(-/-)mice showed delayed axon outgrowth and reduced branching of gustatory axons at embryonic day (E) 13.5. From E14.5 to E18.5, gustatory neurons innervated fewer papillae and completely failed to innervate the mid-region of the tongue in p75(-/-)mice. These early effects of the p75 mutation on gustatory axons preceded the loss of geniculate ganglion neurons starting at E14.5 and also contributed to a loss of taste buds at and after birth. Because knockouts for the TrkB receptor (TrkB(-/-)) do not lose as many taste buds as hybrid knockouts for its two ligands (BDNF and NT4), we asked if p75 maintains those additional taste buds in the absence of TrkB. It does not; hybrid TrkB(-/-)/p75(-/-)mice had more taste buds than TrkB(-/-)mice; these additional taste buds were not due to an increase in neurons or innervation. Conclusions: p75 regulates gustatory neuron axon branching and tongue innervation patterns during taste system development. This function is likely accomplished independently of BDNF, NT4, and TrkB. In addition, p75 does not support the remaining neurons or taste buds in TrkB(-/-)mice.