Coordinated regulation of gene expression by Brn3a in developing sensory ganglia
Coordinated regulation of gene expression by Brn3a in developing sensory ganglia
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DOI：
10.1242/dev.01260
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发表时间：
2004-08-01
期刊：
影响因子：
4.6
通讯作者：
Turner, EE
中科院分区：
文献类型：
--
作者：
Eng, SR;Lanier, J;Turner, EE
缺乏POU结构域转录因子Brn3a的小鼠表现出明显的感觉轴突生长缺陷和异常的感觉细胞凋亡。我们通过对Brn3a突变小鼠的基因芯片分析，确定了Brn3a在发育中的三叉神经节中的调控靶点。这些结果表明，Brn3介导神经递质系统、离子通道、轴突结构成分以及细胞内和细胞内信号系统的协调表达。Brn3a的缺失也会导致转录因子的异位表达，通常在发育早期和神经系统的其他区域都能检测到。杂合子小鼠的靶基因表达是正常的，这与之前的工作一致，表明Brn3a的自动调节导致了基因剂量补偿。对其中几个下游基因表达的详细研究表明，Brn3a在三叉神经节中的调节作用似乎在更多的后部感觉神经节中保守，但在表达该因子的中枢神经元中不存在。
Mice lacking the POU-domain transcription factor Brn3a exhibit marked defects in sensory axon growth and abnormal sensory apoptosis. We have determined the regulatory targets of Brn3a in the developing trigeminal ganglion using microarray analysis of Brn3a mutant mice. These results show that Brn3 mediates the coordinated expression of neurotransmitter systems, ion channels, structural components of axons and inter- and intracellular signaling systems. Loss of Brn3a also results in the ectopic expression of transcription factors normally detected in earlier developmental stages and in other areas of the nervous system. Target gene expression is normal in heterozygous mice, consistent with prior work showing that autoregulation by Brn3a results in gene dosage compensation. Detailed examination of the expression of several of these downstream genes reveals that the regulatory role of Brn3a in the trigeminal ganglion appears to be conserved in more posterior sensory ganglia but not in the CNS neurons that express this factor.