Koudelka Juraj, Horn Jacqueline M, Vatanashevanopakorn Chinnavuth, Minichiello Liliana
Centre for Neuroregeneration, University of Edinburgh, EH16 4SB Edinburgh, UK.
Neural Dev. 2014 Sep 26;9:21. doi: 10.1186/1749-8104-9-21.
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.
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.
神经营养因子-4（NT-4）和脑源性神经营养因子（BDNF）与同一受体Ntrk2/TrkB结合，但在啮齿动物味觉系统发育中发挥不同作用。然而，这些过程背后的机制尚不清楚。
在此，我们在体内证明，TrkB受体上主要衔接蛋白对接位点的单突变或联合点突变会影响小鼠味觉发育的特定方面，已知这些方面依赖于BDNF或NT-4。具体而言，TrkB-SHC对接位点发生突变的小鼠在发育的早期和后期味觉神经元存活率均降低，早期存活率依赖于NT-4，后期存活率依赖于BDNF。此外，这些突变体中舌部神经支配和味蕾形态（均为BDNF依赖性功能）均发生改变。相比之下，单独的TrkB-PLCγ对接位点突变并不影响味觉神经元存活。而且，这些突变体中舌部神经支配延迟，味觉受体表达改变。
我们通过遗传学方法剖析了TrkB受体下游激活的通路，这些通路是由两种神经营养因子NT-4和BDNF控制的味觉系统特定方面所必需的。此外，我们的结果表明TrkB还通过不同的信号通路调节特定味觉受体的表达。这些结果推进了我们对味觉系统生物学的认识，味觉系统是生物体与环境相关的基本感觉系统之一。
