Expression data from neurotrophin transgenic mice

A limited number of growth factors are capable of regulating numerous developmental processes, but how they accomplish this is unclear. In the gustatory system, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) have different developmental roles but exert their effects through the same receptors (TrkB and p75). Using genome wide expression analysis, we determined that BDNF and NT4 also regulate the expression of different sets of genes downstream of receptor signaling in geniculate ganglion. These differences in gene expression likely determine their different roles. BDNF and NT4 could function differently because of temporal or spatial differences of expression or the activation of different signaling pathways. BDNF and NT4 regulate cell death, axonal growth and axonal guidance by altering gene expression. Because many of these functions of the two neurotrophins differ in taste development, each likely alters gene expression in a unique way. To determine if removal of BDNF and NT4 alters gene expression in different ways, I will compare microarray gene expression profiles in the geniculate ganglion among BDNF knockout, Nt4 knockout, and wild type mice during development.仅有少数几类生长因子可调控众多发育进程，但其具体调控机制尚未阐明。在味觉系统中，脑源性神经营养因子（brain-derived neurotrophic factor, BDNF）与神经营养因子4（neurotrophin-4, NT4）虽发挥着不同的发育功能，却通过同一组受体（TrkB与p75）实现信号传导。本研究通过全基因组表达分析发现，在膝状神经节中，BDNF与NT4还可通过受体信号通路调控下游不同的基因表达集。这类基因表达差异大概率决定了二者功能的分化。BDNF与NT4的功能差异，可能源于二者表达的时空分布差异，或是激活了不同的信号通路。BDNF与NT4可通过调控基因表达，参与细胞凋亡、轴突生长及轴突导向等过程。鉴于这两种神经营养因子在味觉发育中的诸多功能存在差异，二者极有可能以各自独特的方式调控基因表达。为明确BDNF与NT4的缺失是否会通过不同方式改变基因表达，本研究将比较发育阶段中BDNF基因敲除、NT4基因敲除及野生型小鼠膝状神经节的基因芯片表达谱。