title: Genetic dissection of TrkB activated signalling pathways required for specific aspects of the taste system.
abstract: BACKGROUND
  Neurotrophin-4 (NT-4) and brain derived neurotrophic factor (BDNF) bind to the same receptor, Ntrk2/TrkB, but play distinct roles in the development of the rodent gustatory system. However, the mechanisms underlying these processes are lacking.
  
  
  RESULTS
  Here, we demonstrate, in vivo, that single or combined point mutations in major adaptor protein docking sites on TrkB receptor affect specific aspects of the mouse gustatory development, known to be dependent on BDNF or NT-4. In particular, mice with a mutation in the TrkB-SHC docking site had reduced gustatory neuron survival at both early and later stages of development, when survival is dependent on NT-4 and BDNF, respectively. In addition, lingual innervation and taste bud morphology, both BDNF-dependent functions, were altered in these mutants. In contrast, mutation of the TrkB-PLCγ docking site alone did not affect gustatory neuron survival. Moreover, innervation to the tongue was delayed in these mutants and taste receptor expression was altered.
  
  
  CONCLUSIONS
  We have genetically dissected pathways activated downstream of the TrkB receptor that are required for specific aspects of the taste system controlled by the two neurotrophins NT-4 and BDNF. In addition, our results indicate that TrkB also regulate the expression of specific taste receptors by distinct signalling pathways. These results advance our knowledge of the biology of the taste system, one of the fundamental sensory systems crucial for an organism to relate to the environment.
authors.forename: Juraj
authors.initials: J
authors.lastname: Koudelka
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Horn
authors.forename: Chinnavuth
authors.initials: C
authors.lastname: Vatanashevanopakorn
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, EH16 4SB Edinburgh, UK. liliana.minichiello@pharm.ox.ac.uk.
authors.forename: Liliana
authors.initials: L
authors.lastname: Minichiello
mesh_terms: D000818:Animals; D005830:Geniculate Ganglion / Q000196:embryology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017354:Point Mutation; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D013649:Taste / Q000235:genetics / Q000502:physiology*; D013650:Taste Buds / Q000196:embryology / Q000378:metabolism; D014059:Tongue / Q000294:innervation
chemical_list: D020813:Receptor, trkB