Eng S Raisa, Dykes Iain M, Lanier Jason, Fedtsova Natalia, Turner Eric E
Department of Psychiatry, University of California, San Diego and VA San Diego Healthcare System, Gilman Drive, La Jolla, CA 92093-0603, USA.
Neural Dev. 2007 Jan 19;2:3. doi: 10.1186/1749-8104-2-3.
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 gene expression, but a subset of Brn3a target genes show increased expression only in the TG. In the wild-type TG these Brn3a-repressed genes are silent, yet their promoter regions exhibit histone H3-acetylation levels similar to constitutively transcribed gene loci. This increased H3-acetylation is not observed in the DRG, suggesting that chromatin modifications play a role in cell-specific target gene regulation by Brn3a.
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.
一般躯体感觉在颅部水平由三叉神经节(TG)传导至中枢神经系统,在脊髓水平由背根神经节(DRG)传导。尽管这些神经节具有相似的功能,但它们有不同的胚胎学起源,即两者都包含源自神经嵴的神经元,而只有TG包含源自基板外胚层的细胞。
在此我们利用对E13.5胚胎的微阵列分析来证明,发育中的DRG和TG具有非常相似的整体基因表达模式。在缺乏POU结构域转录因子Brn3a的小鼠中,DRG和TG在基因表达上表现出许多共同变化,但Brn3a靶基因的一个子集仅在TG中表达增加。在野生型TG中,这些被Brn3a抑制的基因是沉默的,但其启动子区域表现出与组成型转录基因座相似的组蛋白H3乙酰化水平。在DRG中未观察到这种H3乙酰化增加,这表明染色质修饰在Brn3a对细胞特异性靶基因的调控中起作用。
这些结果表明,Brn3a的一个发育作用是抑制在不同轴位水平产生的感觉神经元之间基因表达的潜在差异,并调控发育基因表达的趋同程序,其中功能相似的神经元群体由不同的胚胎学底物产生。