Transcription profiling of mouse spinal and trigeminal sensory ganglia of Brn3a knockout and wild type mice reveals conserved and distinct regulatory targets of Brn3a at different levels of the sensory axis

General somatic sensation is conveyed to the central nervous system at cranial levels by the trigeminal ganglion (TG), and at spinal levels by the dorsal root ganglia (DRG). Although these ganglia have similar functions, they have distinct embryological origins, in that both contain neurons originating from the neural crest, while only the TG includes cells derived from the placodal ectoderm. Here we use microarray analysis of E13.5 embryos to demonstrate that the developing DRG and TG have very similar overall patterns of gene expression. In mice lacking the POU-domain transcription factor Brn3a the DRG and TG exhibit many common changes in downstream gene expression, but a subset of genes show increased expression only at cranial levels. Although silent in wild-type ganglia, the promoter regions of genes which are activated in the absence of Brn3a also exhibit increased histone H3-acetylation at levels similar to constitutively transcribed gene loci, and this H3-acetylation is tissue-specific for genes which are increased only in the TG. These results demonstrate that one developmental role of Brn3a is to repress potential differences in gene expression between sensory neurons generated at different axial levels, and to regulate a convergent program of developmental gene expression, in which functionally similar populations of neurons are generated from different embryological substrates. Experiment Overall Design: Microarrays used to compare the patterns of gene expression in the dorsal root ganglia and trigeminal ganglia of Brn3a knockout and wild-type mice. Embryonic day 13.5 (E13.5) was chosen because at this point in development mutant mice exhibit major defects in sensory axon growth, but have yet to undergo the period of extensive sensory neuron death associated with later stages.一般躯体感觉信号经三叉神经节（trigeminal ganglion, TG）向中枢神经系统传递颅段信息，而脊髓段的信号传递则由背根神经节（dorsal root ganglia, DRG）完成。尽管两类神经节功能相近，但其胚胎起源存在显著差异：二者均包含源自神经嵴的神经元，但仅三叉神经节（TG）含有来源于板外胚层的细胞。 本研究通过对胚胎发育第13.5天（E13.5）的小鼠胚胎开展基因芯片分析，证实发育中的背根神经节（DRG）与三叉神经节（TG）的整体基因表达模式高度相似。在缺失POU结构域转录因子Brn3a的小鼠中，DRG与TG的下游基因表达均出现诸多共同变化，但存在一类基因仅在颅段神经节中表达上调。 尽管在野生型神经节中此类基因处于沉默状态，但在Brn3a缺失条件下被激活的基因，其启动子区域的组蛋白H3乙酰化水平与组成性转录的基因位点相当；且仅在TG中表达上调的基因，其组蛋白H3乙酰化表现出组织特异性。 上述结果表明，Brn3a的一项发育功能是抑制不同轴水平来源的感觉神经元之间基因表达的潜在差异，并调控一套趋同的发育基因表达程序——即从不同胚胎底物中产生功能相似的神经元群体。 实验整体设计：本研究利用基因芯片技术比较Brn3a敲除型与野生型小鼠的背根神经节（DRG）及三叉神经节（TG）的基因表达模式。选择胚胎发育第13.5天（E13.5）作为研究节点，是因为在此发育阶段，突变小鼠已出现感觉轴突生长的显著缺陷，但尚未进入与后续发育阶段相关的大规模感觉神经元死亡时期。