Neural development

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1749-810492014Sep26Neural developmentNeural DevGenetic dissection of TrkB activated signalling pathways required for specific aspects of the taste system.212110.1186/1749-8104-9-21Neurotrophin-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.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.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.KoudelkaJurajJHornJacqueline MJMVatanashevanopakornChinnavuthCMinichielloLilianaLCentre for Neuroregeneration, University of Edinburgh, EH16 4SB Edinburgh, UK. liliana.minichiello@pharm.ox.ac.uk.engR01DC009418DCNIDCD NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20140926

EnglandNeural Dev1012865741749-8104EC 2.7.10.1Receptor, trkBIMAnimalsGeniculate GanglionembryologymetabolismMaleMiceMice, Inbred C57BLMice, TransgenicPoint MutationReceptor, trkBgeneticsmetabolismSignal TransductiongeneticsTastegeneticsphysiologyTaste BudsembryologymetabolismTongueinnervation2014732014918201492760201492760201537602014926epublish25256039PMC417816210.1186/1749-8104-9-211749-8104-9-21Fan G, Egles C, Sun Y, Minichiello L, Renger JJ, Klein R, Liu G, Jaenisch R. Knocking the NT4 gene into the BDNF locus rescues BDNF deficient mice and reveals distinct NT4 and BDNF activities. Nat Neurosci. 2000;3(4):350–357. doi: 10.1038/73921.10.1038/7392110725924Huang T, Krimm RF. BDNF and NT4 play interchangeable roles in gustatory development. Dev Biol. 2014;386(2):308–320. doi: 10.1016/j.ydbio.2013.12.031.10.1016/j.ydbio.2013.12.031PMC395034924378336Jones KR, Fariñas I, Backus C, Reichardt LF. 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