PMID- 25256039 OWN - NLM STAT- MEDLINE DCOM- 20150306 LR - 20211021 IS - 1749-8104 (Electronic) IS - 1749-8104 (Linking) VI - 9 DP - 2014 Sep 26 TI - Genetic dissection of TrkB activated signalling pathways required for specific aspects of the taste system. PG - 21 LID - 10.1186/1749-8104-9-21 [doi] AB - 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-PLCgamma 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. FAU - Koudelka, Juraj AU - Koudelka J FAU - Horn, Jacqueline M AU - Horn JM FAU - Vatanashevanopakorn, Chinnavuth AU - Vatanashevanopakorn C FAU - Minichiello, Liliana AU - Minichiello L AD - Centre for Neuroregeneration, University of Edinburgh, EH16 4SB Edinburgh, UK. liliana.minichiello@pharm.ox.ac.uk. LA - eng GR - R01DC009418/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140926 PL - England TA - Neural Dev JT - Neural development JID - 101286574 RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Geniculate Ganglion/*embryology/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Point Mutation MH - Receptor, trkB/genetics/*metabolism MH - Signal Transduction/*genetics MH - Taste/genetics/*physiology MH - Taste Buds/embryology/metabolism MH - Tongue/innervation PMC - PMC4178162 EDAT- 2014/09/27 06:00 MHDA- 2015/03/07 06:00 PMCR- 2014/09/26 CRDT- 2014/09/27 06:00 PHST- 2014/07/03 00:00 [received] PHST- 2014/09/18 00:00 [accepted] PHST- 2014/09/27 06:00 [entrez] PHST- 2014/09/27 06:00 [pubmed] PHST- 2015/03/07 06:00 [medline] PHST- 2014/09/26 00:00 [pmc-release] AID - 1749-8104-9-21 [pii] AID - 10.1186/1749-8104-9-21 [doi] PST - epublish SO - Neural Dev. 2014 Sep 26;9:21. doi: 10.1186/1749-8104-9-21.